gene_name
string
gene_id
string
category
string
cell_name
string
tissue_type
string
phenotype
string
aging_type
string
experiment
string
description
string
target_gene
string
regulatory_type_of_target_gene
string
target_gene_experiment
string
target_gene_description
string
regulatory_pathway
string
regulatory_type_of_pathway
string
pathway_experiment
string
pathway_description
string
species
string
experimental_category
string
aging_characteristic
string
pmid
int64
source
string
Alizarin_red_S_staining
int64
Annexin_V_binding_assay
int64
Apoptosis_assay
int64
Atomic_force_microscopy_imaging
int64
Autofluorescence
int64
Behavioral_assessment
int64
BrdU_analysis
int64
BrdU_assay
int64
CCK_8_assay
int64
CHIP
int64
Cell_activity_assay
int64
Cell_apoptosis_assay
int64
Cell_counting
int64
Cell_cycle_analysis
int64
Cell_growth_assay
int64
Cell_migration_assay
int64
Cell_morphological_analysis
int64
Cell_proliferation_assay
int64
Cell_transfection
int64
Cell_viability_assay
int64
ChIP_qPCR
int64
Clonal_expansion_assay
int64
Clonogenic_assay
int64
Colony_formation_assay
int64
Colony_formation?assay
int64
Comet_assay
int64
Crystal_violet_assay
int64
Cytokine_assay
int64
DAPI_staining
int64
DNA_FISH
int64
DNA_fiber_assay
int64
ELISA
int64
EdU_Assay
int64
EdU_assay
int64
EdU_assay/SA__gal_activity_assay
int64
EdU_cell_proliferation_assay
int64
FACS_analysis
int64
FCM_analysis
int64
FISH
int64
FITC_Annexin_V/PI
int64
Flow_cyotmetry
int64
Flow_cytometry
int64
Fluorescence_quenching_assay
int64
GO_analysis
int64
GSEA_analysis
int64
Giemsa_staining
int64
Growth_curve_assay
int64
Growth_kinetics_analysis
int64
Histochemical_staining
int64
Histological_images_analysis
int64
Histological_staining
int64
Hoechst_staining
int64
IHC
int64
IHC_staining
int64
Immunoblotting
int64
Immunochemical_staining
int64
Immunocytochemistry
int64
Immunofluorescence
int64
Immunohistochemical_staining
int64
Immunohistochemistry
int64
Immunostaining
int64
Immunostainings
int64
JC_1_probe_staining
int64
Ki67_staining
int64
Knockdown
int64
LDH_activity_assay
int64
Lifespan_assay
int64
Luciferase_reporter_assay
int64
MTS_assay
int64
MTT_assay
int64
Microarray
int64
Northern_blot
int64
PCR
int64
PI_staining
int64
Prevent
int64
RNA_seq
int64
ROS_assay
int64
ROS_staining
int64
RT__PCR
int64
RT_PCR
int64
RT_qPCR
int64
SA__Gal_activity_assay
int64
SA__gal_activity
int64
SA__gal_activity_assay
int64
SA__gal_staining
int64
SAHF
int64
Safranin_O_fast_green_staining
int64
Safranin_O/Fast_Green_staining
int64
Safranin_O
int64
Southern_Blot
int64
Southern_blot
int64
Southern_blot_analysis
int64
Southern_hybridization
int64
Southern_hybridization_analysis
int64
Survival_curve
int64
TRAP_assay
int64
TRF_analysis
int64
TRF_assay
int64
TUNEL_assay
int64
Telomerase_Assay
int64
Telomerase_activity_assay
int64
Telomerase_assay
int64
Telomere_length_assay
int64
Transmission_electron_microscopy
int64
Transwell_assay
int64
Trypan_blue_staining
int64
Tube_formation_assay
int64
WST_1_assay
int64
WST_8_assay
int64
Western_blot
int64
XTT_assay
int64
miRNA_qRT_PCR
int64
qPCR
int64
qPT_PCR
int64
qRT_PCR
int64
qRT¨CPCR
int64
¦ÃH2AX_staining
int64
FOXO1
2308
protein coding
CD8+T
--
Aging
Prevent
Cytokine assay//Flow cytometry
In Foxo1-KO T cells, CD28 was uniformly reduced in naive T cells, and it was even more reduced in P14 Foxo1-KO KLRG1low day 30 post-infection T cells, compared with WT. A further indication of senescence is the inability of T cells to produce effector cytokines upon stimulation: TNF, IFN-¦Ã, and interleukin-2 (IL-2). T...
BACH2//AP-1
Upregulation//Downregulation
CHIP-Seq//ATAC-seq//qRT-PCR
We found that FOXO1 exhibited genomic binding within and proximal to the Bach2 gene locus at multiple sites in naive and day 12 p.i. cells. We observed that Bach2 becomes FOXO1 dependent only post-activation. Whereas naive WT and Foxo1-KO cells had similar, abundant Bach2 mRNA expression, 7 and 12 days post-activation ...
--
--
--
--
Human
HL
cellular senescence
33,503,413
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
YAP1
10413
protein coding
SW 1353,Hs 819.T,Chondrocyte
knee
Chondrosarcoma
Prevent
Atomic force microscopy imaging//EdU assay//SA--gal activity assay
YAP1 knockdown significantly increased the percentage of senescence-associated ¦Â-galactosidase (SA-¦Â-gal)-positive cells in the two different CHS cell strains, including SW 1353 and Hs 819.T. AFM confirmed that knockdown of YAP1 increased the chondrocyte¡¯s elastic modulus, a characteristic of senescent cells, at the...
p21
Downregulation
Western blot//SA-¦Â-gal activity assay
Notably, loss of YAP1 dramatically upregulated the expression of p21 in the SW 1353 cells, regardless of cell density. As expected, overexpression of HA-YAP1-5SA upregulated the expression of its target gene Cyr61 and, reduced p21 expression and p21-induced cellular senescence in cells expressing shYAP1#4 but not SC.
YAP-p21
Downregulation
Western blot//Immunofluorescence
A lower concentration of VP significantly upregulated p21 expression and increased the percentage of senescent cells, while a higher concentration of VP suppressed the p21 expression, accompanied by pronounced cell apoptosis. Indeed, knockdown of p21 by sip21#3 and sip21#4 remarkably abolished the cell senescence induc...
Human
HL
cellular senescence
33,495,462
Gene
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
RPPH1
85495
ncRNA
WI-38,IDH4
--
Aging
Accelerate
Flow cytometry//SA--gal activity assay
Seven days after transfection, senescence associated ¦Â-galactosidase staining revealed that RPPH1 RNA overexpression promotes activation of acidic ¦Â-galactosidase as a marker of cellular senescence. Measurement of cell division cycle by Propidium Iodide (PI) and Flow Cytometry uncover that RPPH1 RNA overexpression ar...
MLC1 mRNA//CCR7 mRNA
Upregulation
qRT-PCR//RNA-seq
Prediction of partial complementarity was tested in MS2-tagged RNA affinity purification assay, confirming that MLC1 and CCR7 mRNAs are biochemically associated with RPPH1 RNA in proliferating fibroblasts but not senescent ones. In addition, we observed that MLC1 and CCR7 mRNAs are destabilized in senescent fibroblasts...
--
--
--
--
Human
HL
cellular senescence
33,466,722
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CLIC1
1192
protein coding
HUVECs
--
Aging
Accelerate
qRT-PCR
Upregulating CLIC1 in HUVECs promoted cell senescence, evidenced by the mRNA levels of p16, PAI-1, and Sirt1. However, CLIC1 silencing decreased H2O2 induced cellular senescence.
Nrf2
Downregulation
Western blot//Immunofluorescence
The findings revealed that even though H2O2 slightly induced nuclear translocation of Nrf2, IAA94 treatment or CLIC1 knockdown significantly increased Nrf2 translocation in H2O2-treated HUVECs. Nuclear levels of the Nrf2 protein were determined by Western blot analysis. H2O2 increased the nuclear protein expression lev...
Nrf2-HO1//AMPK-AKT-GSK3¦Â
Downregulation
Western blot
Overexpression of CLIC1 inhibited the activation of the Nrf2/HO-1 pathway and promoted oxidative stress injury in HUVECs. IAA-94 treatment activated the AMPK/AKT/GSK3¦Â pathway while CLIC1 knockdown enhanced the expresson of p-AMPK/total AMPK. However, CLIC1 overexpression significantly decreased the ratio of p-AMPK Th...
Human
L
cellular senescence
33,432,550
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
SMAD4
4089
protein coding
Fibroblast
--
Aging
Prevent
qRT-PCR
Next, we assessed expression of cellular senescence and proliferative markers, including p16, p21, and Ki67. The mRNA levels of p16 and p21 were increased > 4-fold and > 5-fold, respectively, in mutant compared to control or SMAD4-WT cells. Consistent with this, expression of the proliferative marker Ki67 was substanti...
--
--
--
--
TGF-¦Â/SMAD-IFN¦Ã
Activation
qRT-PCR//SA-¦Â-gal activity assay
Consistent with this, the growth curve of Werner cells displayed an increased doubling time with passage compared to control normal fibroblasts. At passage 14, the population doubling time of Werner cells was markedly increased compared to corresponding controls, suggesting proliferative arrest and accelerated senescen...
Human
L
cellular senescence
33,428,109
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
MT-CO2
4513
protein coding
HMSCs
--
Aging
Prevent
SA--gal activity assay//WST-1 assay
The results of WST-1 assay revealed that the COX2 transfectants grew at a faster rate than the normal HMSCs. SA-¦Â-Gal staining revealed that the overexpression of COX2 significantly delayed the aging process of HMSCs.
--
--
--
--
--
--
--
--
Human
L
cellular senescence
33,416,107
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
MIR217
406999
ncRNA
HUVECs
--
Aging
Accelerate
SA--gal activity assay
The data showed that overexpression of miR-217 significantly increased the proportion of SA-¦Â-gal positive cells in PDL12, PDL16 and PDL20 cells
SIRT1
Downregulation
qRT-PCR//Western blot
Western blot and RT-qPCR results showed that up-regulation of miR-217 in PDL8 cells significantly inhibited SIRT1 expression, whereas miR-217 inhibitor significantly inhibited SIRT1 expression in PDL44 cells.
SIRT1-p53
Activation
qRT-PCR//Western blot
SIRT1 protein levels and mRNA levels were significantly lower in senescent PDL44 HUVECs than in young PDL8 HUVECs, while p53 protein levels and mRNA levels were significantly higher in senescent PDL44 HUVECs than in young PDL8 HUVECs
Human
L
cellular senescence
33,392,891
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
TWIST1
7291
protein coding
NP Cells
Nucleus pulposus
Disc degeneration
Prevent
CCK-8 assay//SA--gal activity assay//Western blot//qRT-PCR
Of note, in the TWIST overexpression group, the p53 and p21 protein were effectively suppressed compared to the TNF-¦Á group. In addition, the collagen II and ¦Â-gal protein expression were determined by IF staining. However, TWIST1/2 overexpressed NP cells were partly efficient in inhibiting the MMP-13 and IL-1¦Â upre...
--
--
--
--
p53-p21
Downregulation
Western blot
Of note, in the TWIST overexpression group, the p53 and p21 protein were effectively suppressed compared to the TNF-¦Á group. Besides, the p53 and p21 levels were inhibited due to the supplement of TWIST protein.
Human
L
cellular senescence
33,378,011
Gene
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
TWIST2
117581
protein coding
NP Cells
Nucleus pulposus
Disc degeneration
Prevent
CCK-8 assay//SA--gal activity assay//Western blot//qRT-PCR
Of note, in the TWIST overexpression group, the p53 and p21 protein were effectively suppressed compared to the TNF-¦Á group. In addition, the collagen II and ¦Â-gal protein expression were determined by IF staining. However, TWIST1/2 overexpressed NP cells were partly efficient in inhibiting the MMP-13 and IL-1¦Â upre...
--
--
--
--
p53-p21
Downregulation
Western blot
Of note, in the TWIST overexpression group, the p53 and p21 protein were effectively suppressed compared to the TNF-¦Á group. Besides, the p53 and p21 levels were inhibited due to the supplement of TWIST protein.
Human
L
cellular senescence
33,378,011
Gene
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
CDK2
1017
protein coding
Phoenix-Eco
--
Leukemia
Prevent
Immunofluorescence//Immunohistochemistry//SA--gal activity assay//Western blot
Although samples from both CVT2584- and vehicle-treated mice showed a certain degree of positivity, the SA-¦Â-gal staining was significantly increased in spleens from CVT2584-treated mice, as quantitated in Figure 5. We also examined the presence of senescence-associated heterochromatin foci (SAHF), using an antibody d...
MYC
Upregulation
Western blot
In agreement with our previous report, reduced MYC Ser-62 phosphorylation was observed in CVT2584-treated compared with vehicle-treated animals, both at lower and higher doses of CVT2584, supporting the notion that CDK2 regulates MYC phosphorylation in vivo.
--
--
--
--
Human
L
cellular senescence
33,356,836
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
CFL1
1072
protein coding
WI-38
--
Aging
Accelerate
Immunofluorescence//SA--gal activity assay//Western blot
Subsequently, we assessed the expression of the cell cycle inhibitors involved in senescence©\associated growth arrest. We found that the over©\expression of cofilin©\1 in young cells could induce p53, p21Cip1, p27Kip1, p16INK4, and p©\cofilin©\1, but the silencing of cofilin©\1 in senescent cells suppressed these mole...
TEAD1
Downregulation
qRT-PCR
To investigate whether the down©\regulation of TEAD1 mRNA is associated with up©\regulated cofilin©\1 in senescent cells, we silenced cofilin©\1 and found that the TEAD1 mRNA levels were restored in senescent cells. Additionally, the over©\expression of cofilin©\1 could suppress the expression of TEAD1 transcripts and ...
--
--
--
--
Human
L
cellular senescence
33,336,885
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
GATA6
2627
protein coding
iPSC-MSC
--
Aging
Accelerate
SA--gal activity assay//qRT-PCR
GATA6 knockdown in cells at the late passage significantly reduced the ratio of senescent to total cells whereas that in cells at the early passage did not. Similarly, GATA6 knockdown markedly decreased the expression of p53 and p21CIP1 and significantly increased the expression of CDK1 in late-passage cells but did no...
--
--
--
--
SHH-FOXP1
Downregulation
SA-¦Â-gal activity assay//Western blot
Knockdown of GATA6 resulted in an increase in the expression of the SHH signaling molecule SHH, SMO, and GLI1 as well as FOXP1, suggesting that GATA6 is an upstream inhibitory regulator of both SHH signaling and FOXP1. When the expression of SMO, a key molecule in the SHH pathway, was repressed, the expression of its d...
Human
HL
cellular senescence
33,252,174
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
PDK1
5163
protein coding
NHDF
--
Aging
Accelerate
EdU assay//SA--gal activity assay//qRT-PCR
Either PDK1 inhibition or dual inhibition of mTOR and NF-¦ÊB reduced the SA-¦Â-gal¨Cpositive cell population from >80% to <40%, whereas mTOR inhibition alone did not significantly alter the percent of SA-¦Â-gal¨Cpositive cells. We found that the percent of proliferating cells increased after either PDK1 inhibition or d...
mTOR//NF-¦ÊB
Upregulation
qRT-PCR//EdU assay
We found that the percent of proliferating cells increased after either PDK1 inhibition or dual inhibition of mTOR and NF-¦ÊB, but not after only mTOR inhibition. Senescent cells showed a significantly increased expression of these SASP-associated genes. Either exposure to the NF-¦ÊB inhibitor JSH23 or the PDK1 inhibi...
--
--
--
--
Human
HL
cellular senescence
33,229,519
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
SLX4IP
128710
protein coding
DU145,PC-3
--
CRPC
Prevent
SA--gal activity assay//Western blot
As expected, a considerable increase in the proportion of senescence-associated ¦Â-galactosidase (SA ¦Â-gal) staining was observed in late-passage cells with SLX4IP knockdown compared with late-passage controls. Elevations in relative p21 protein expression, a senescence-associated marker, further corroborated the sene...
--
--
--
--
--
--
--
--
Human
L
telomere attrition
33,188,147
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
MEG3
55384
ncRNA
A549,MCF-7
--
Aging
Accelerate
SA--gal activity assay//Western blot//qRT-PCR
The degree of senescence of A549 and MCF-7 cells was detected by SA-¦Â-gal staining after depletion of lncRNA MEG3, showing a significant decrease compared with that of the control group. Next, we induced senescence by etoposide after overexpression of lncRNA MEG3 in A549 and MCF-7 cells, and increased expression of p2...
miR-16-5p
Binding
Dual-Luciferase reporter assay
The results showed that the luciferase activity decreased significantly in Hek293T cells co-transfected with wild type lncRNA MEG3 and miR-16-5p mimics, whereas luciferase activity was restored in cells co-transfected with mutant lncRNA MEG3 and miR-16-5p mimics, indicating that miR-16-5p is indeed a direct target gene...
miR-16-5p-VGLL4
Activation
qRT-PCR//SA-¦Â-gal activity assay
Moreover, silencing lncRNA MEG3 or VGLL4 significantly alleviated low dose etoposide induced senescence, as demonstrated by decreased p21 and p16 expression and SA-¦Â-gal staining positive cells. Interestingly, the effect of the inhibition of lncRNA MEG3 on the senescence of tumor cells was prominently abolished by the...
Human
HL
cellular senescence
33,141,998
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
NEAT1
283131
ncRNA
BM-MSC
--
Aging
Prevent
SA--gal activity assay//qRT-PCR
QRT-PCR results suggested that exosomeMIF transferred LncRNA¨CNEAT1 to cardiomyocytes, while silencing LncRNA¨CNEAT1 in MSCs blocked the transfer process. In the subsequent experiments, exosomeMIF significantly reduced the percentage of cells in the G0/G1 phase, expression of p27 and p16, and number of SA-¦Â-gal-positi...
miR-221-3p
Binding
Dual-Luciferase reporter assay//qRT-PCR//SA-¦Â-gal activity assay
LncRNA¨CNEAT1 contains the binding site for miR-221-3p, suggesting that lncRNA as a ceRNA sponged miR-221-3p to limit its function, which was confirmed by dual-luciferase gene reporter assay. As illustrated in Fig. 6b, the co-transfection of miR-221-3p significantly inhibited the luciferase activities elicited by LncRN...
--
--
--
--
Human
HL
cellular senescence
33,129,330
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
HEIH
100859930
ncRNA
OVCA429,OVCA433,OVCAR3
--
Ovarian cancer
Prevent
SA--gal activity assay
As shown in Fig. 2H, the percentage of SA-b-Gal-positive cells was increased by HEIH knockdown in OVCA429 (sh-HEIH#1: 5.2-fold higher than sh-NC group; sh-HEIH#2: 4.6-fold higher than sh-NC group) and OVCA433 cells (sh-HEIH#1: 4.8-fold higher than sh-NC group; shHEIH#2: 4.7-fold higher than sh-NC group).
miR-3619-5p
Binding
Dual-Luciferase reporter assay//qRT-PCR//RIP
From Figure 3D, the transfection of miR-3619-5p mimics showed no difference on the luciferase activity of pmirGLO-HEIH-Mut vectors, but significantly decreased the luciferase reporter activity of pmirGLO-HEIHWt vectors in OVCA429 (0.33-fold decreased) and OVCA433 cells (0.41-fold decreased) (n ? 3, P < 0.05). In additi...
miR-3619-5p-CTTNBP2
Downregulation
Dual-Luciferase reporter assay//qRT-PCR//RIP
As presented in Figure 5C, the luciferase reporter activity of pmirGLO-CTTNBP2-Wt vectors was significantly reduced by miR-3619-5p mimics transfection (OVCA433: 0.38-fold decreased; OVCA429: 0.44-fold decreased). RIP assay indicated that miR-3619-5p (OVCA429: 785-fold increased; OVCA433: 833-fold increased) and CTTNBP2...
Human
L
cellular senescence
33,110,047
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
SNHG29
125144
ncRNA
HTR8/SVneo
--
Preterm birth
Accelerate
SA--gal activity assay//qRT-PCR
SA-¦Â-Gal increased in the SNHG29 + H2O2 cells as compared to the NC + H2O2 cells (7.8%, 15.9% and 23% respectively). We measured the levels of pro-inflammatory cytokines, such as IL-8 and TNF- ¦Á. The mRNA levels of IL-8 and TNF-¦Á decreased in cells depleted of SNHG29 compared with NC-Si and NC-Si + H2O2 cells. Howev...
--
--
--
--
p53-p21
Activation
Western blot//SA-¦Â-gal activity assay//qRT-PCR
Treated cells depleted of SNHG29 (si-SNHG29 + H2O2) showed a reduction in the levels of mRNA of p53 and p21, and the protein levels of p53, phospho-p53,p21and phospho-p21, as compared to treated cells with wild-type SNHG29. Overexpression of SNHG29 in H 2O2-treated cells (SNHG29 + H2O2) showed increases in the level of...
Human
L
cellular senescence
33,080,448
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
METTL3
56339
protein coding
hMSCs
--
Progeroid syndromes
Prevent
Clonal expansion assay//SA--gal activity assay
Furthermore, METTL3-deficient hMSCs acquired premature aging phenotypes, as evidenced by decreased proliferative capacity and increased percentage of SA-¦Â-Gal-positive cells. Moreover, enhanced cell proliferative capacity and reduced SA-¦Â-Gal-positive cells were observed in HGPS and WS hMSCs upon METTL3 overexpressio...
MIS12
Downregulation
qRT-PCR//Western blot
Among these transcripts, we noticed that m6A modifications in MIS12, a key regulator of cell proliferation, were markedly reduced in both prematurely senescent and METTL3-deficient hMSCs, as validated by MeRIP-qPCR analysis. We also detected a significant decrease in MIS12 expression at both the mRNA and protein levels...
--
--
--
--
Human
HL
cellular senescence
33,035,345
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
HES1
3280
protein coding
Dermal fibroblasts
Skin
Aging
Prevent
Clonal expansion assay//SA--gal activity assay
Ectopic overexpression or CRISPR-dCas9-mediated endogenous activation of HES1 protected human fibroblasts against aging phenotypes, evidenced by increased cell proliferation and attenuated cell senescence
--
--
--
--
--
--
--
--
Human
HL
cellular senescence
33,238,152
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
KLF6
1316
protein coding
Dermal fibroblasts
Skin
Aging
Prevent
Clonal expansion assay//ELISA//SA--gal activity assay//qRT-PCR
Senescence-associated ¦Â-galactosidase (SA-¦Â-gal) staining showed that knockdown of KLF6 promoted senescence of human primary epidermal keratinocytes In addition, the downregulation of KLF6 in human primary keratinocytes led to decreased proliferation ability and increased expression and secretion of pro-inflammatory ...
--
--
--
--
--
--
--
--
Human
HL
cellular senescence
33,238,152
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
PPARA
5465
protein coding
EA.hy926,HUVEC
--
Atherosclerosis
Prevent
Immunostainings//SA--gal activity assay
¦Â-gal staining showed that the number of senescent cells decreased after administration of the PPAR¦Á agonist.Immunofluorescence double labeling staining showed that there were a large number of aging endothelial cells in the atherosclerotic plaque of Apoe-/- mice, and the PPAR¦Á agonist inhibited the denudation and m...
GDF11
Binding
EMSA//Dual-Luciferase reporter assay
The EMSA results showed that PPAR¦Á bound to the labeled target probe, and partially to the mutant probe, indicating that PPAR¦Á could bind to the GDF11 target sequence and participate in the regulation of downstream gene transcription. Double-luciferase reporter gene experiment results indicated that PPAR¦Á could bind...
--
--
--
--
Human
L
cellular senescence
33,728,018
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
SGK1
6446
protein coding
Glial cell
--
Parkinson disease
Accelerate
CCK-8 assay//ELISA//RNA-seq//SA--gal activity assay
Second, our RNA©\seq data show that treating glia with an SGK1 inhibitor downregulated the pro©\oxidant Cyba, Ncf2, Recql4, Bax, and Fdxr and senescence©\associated secretory phenotype (SASP) genes. We further observed that senescence©\associated ¦Â©\galactosidase (SA©\¦Â©\gal) activity, the hallmark senescence biomark...
--
--
--
--
--
--
--
--
Human
HL
delay aging
33,646,633
Gene
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
LINC00858
170425
ncRNA
HCT116
Colon cancer tissues
Colorectal cancer
Prevent
SA--gal activity assay
The results of ¦Â-gal staining, immunofluorescence staining, and Western blot analysis demonstrated that the senescence and autophagy of cells treated with sh-NC + sh-WNK2 were reduced in parallel with diminished expression of Beclin-1 and LC3II/I, in contrast to findings in cells treated with sh-NC + sh-NC (p < 0.05)....
WNK2
Upregulation
Western blot
The results from Western blot analysis showed that, compared with cells treated with sh-NC (of WNK2) + sh-NC (of LINC00858), WNK2 expression was reduced in cells treated with sh-NC + sh-WNK2, while its expression was elevated in cells treated with sh-LINC00858 + sh-WNK2 when compared with cells treated with sh-NC + sh-...
--
--
--
--
Human
HL
apoptosis
32,768,499
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CD70
970
protein coding
T cell
--
Aging
Accelerate
Flow cytometry
To investigate the potential role of CD70 signaling in T-cell aging, we examined the expression of CD70 on T cells from 217 healthy adults using flow cytometry. The results showed that CD70-expressing CD4+ and CD8+T cells accumulated with aging.The TCM, TEM, and TEMRA subsets of both CD4+ and CD8+ T cells, known as ant...
--
--
--
--
--
--
--
--
Human
L
delay aging
32,559,178
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
SETMAR
6419
protein coding
U87MG,SF268
--
Glioblastoma
Prevent
Cell transfection//SA--gal activity assay//Western blot
According to experiments, shRNA (sh1) or siRNA (mixture of 3 siRNAs) mediated knockdown of SETMAR initially induced cell death of RR cells; however, eventually (12 days post induction of shRNA and 10-day post siRNA treatment) the cells ceased to grow and became senescent. Importantly, SETMAR knockdown did not alter the...
--
--
--
--
--
--
--
--
Human
HL
delay aging
32,458,986
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
CD9
928
protein coding
HUVEC
--
Aging
Accelerate
Cell transfection//Flow cytometry//SA--gal activity assay//Western blot
To examine the roles of CD9 in endothelial cell senescence, we measured the effects of CD9 knockdown in senescent HUVECs (PD>50). Knockdown of CD9 in senescent cells with siRNA reduced the p53 and p21 levels, representative senescence markers, and the pAKT and pS6K levels, decreased SA¦ÂG staining, and caused morpholog...
--
--
--
--
PI3K-AKT-mTOR-p53
Activation
Cell transfection//SA-¦Â-gal activity assay//Flow cytometry//Western blot
Therefore, we tested whether the PI3K/AKT-mTOR pathway plays a role in CD9-induced senescence. Pretreatment with LY294002, a specific inhibitor of PI3K, or rapamycin, an inhibitor of mTOR, reduced the levels of p53 and p21 and SA-¦Â-gal staining induced by CD9 overexpression. We next tested whether PIK3CA 110¦Â or PIK3...
Human
L
cellular senescence
32,346,137
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
FBP1
2203
protein coding
HSC
--
Aging
Accelerate
Flow cytometry//SA--gal activity assay//¦ÃH2AX staining
Importantly, SA-¦Â-Gal+ cells colocalized with those positive for ¦Á-SMA (an activated HSC maker), and IL6 (prominent SASP component), and significant percentage of ¦Á-SMA+?HSCs also expressed the DNA damage marker ¦Ã-H2AX, collectively supporting the presence of senescent HSCs. As DEN is not usually fibrogenic in mice...
HMGB1
Upregulation
IF//Immunoblotting
We therefore treated DEN/GFP or DEN/Cre animals with inflachromene (ICM), a small molecule shown to block HMGB1 release45. ICM treatment greatly reduced not only surface tumours, but also microscopic lesions in DEN/Cre mice. ICM did not affect hepatic steatosis, based on comparable TG levels. As expected, cytosolic HMG...
--
--
--
--
Human
HL
cellular senescence
32,367,049
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
WISP1
8840
protein coding
Chondrocyte
Cartilage tissues
Osteoarthritis
Prevent
FITC-Annexin V/PI//IHC//SA--gal staining
Normal cartilage specimen ?showed very low expression levels of WISP1. The ?protein levels of WISP1 were significantly increased within ?the middle and deep regions of all detected pathological ?cartilage sections.The optical density analyses showed that OA pa?tients appeared to exhibit a higher WISP1 expression in joi...
--
--
--
--
--
--
--
--
Human
L
apoptosis
33,646,053
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
PPAR
5465
protein coding
--
Great saphenous vein wall
Chronic venous disorder
Prevent
Immunohistochemical staining//RT-qPCR
We studied the gene and protein expression of ¦Á, ¦Â/¦Ä and ¦Ã PPAR isoforms in venous wall from CVeD patients and HV controls. We observed a significant decrease in PPAR-¦Á gene expression by RT-qPCR in CVeD patients with respect to HV controls (HV=5.224 [3.659-8.039] RQ vs CVeD=4.632 [2.365-6.387] RQ, ***p=0.0004). W...
PPAR-¦Á//PPAR-¦Â/¦Ä//TFEB
Downregulation//Downregulation//Downregulation
Immunohistochemical staining//qPCR
We observed a significant ?decrease in PPAR-¦Á gene expression by RT-qPCR in ?CVeD patients with respect to HV controls.//The score for ?PPAR-¦Â/¦Ä was significantly lower for patients with ?CVeD.//Our results showed that the gene expression of ?TFEB was significantly decreased in CVeD patients ?compared with the HV gr...
--
--
--
--
Human
HL
cellular senescence
33,645,625
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
RECQL4
9401
protein coding
KYSE30,KYSE450,KYSE410,KYSE150,TE-1
ESCC tissues
Esophageal cancer
Accelerate
SA--gal activity assay//Western blot
Approximately 45% of KYSE30 RECQL4-depleted cells and 30% of TE-1 RECQL4-depleted cells showed positive SA-¦Â-gal staining. The expression of p21, an effector molecule of G1 arrest and cellular senescence, was also increased significantly, which is consistent with previous studies.
c-myc//cyclinD//CDK6//cyclinE
Downregulation//Downregulation//Upregulation//Upregulation
Western blot
To further investigate how RECQL4 regulates G1/S phase ?transition and cellular senescence, we determined the expres?sion of other related proteins. Depletion of RECQL4 led to decreased expression of c-myc, cyclin D, ?CDK6, and cyclin E.
--
--
--
--
Human
HL
cellular senescence
33,628,589
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
ATM
472
protein coding
HFMs
Human haired scalp
Aging
Prevent
Cell viability assay//IHC//Western blot
The intensity and the distribution level of the staining of TRP-1 and GP100 was higher in the hair ?follicle melanocytes of fully pigmented follicles, sporadic in melanocytes with reduced pigmentation and lack?ing in weakly pigmented/white hair follicles.Results showed increased total ATM levels in HFMs afer H2O2 treat...
--
--
--
--
--
--
--
--
Human
L
apoptosis
33,128,003
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
SENEX
93663
protein coding
OCI©\LY8
--
r/r DLBCL
Accelerate
SA--gal activity assay
Interestingly, compared with the control group (C group) and scramble negative control (NC group), the senescence rate and proliferation rate were significantly decreased (Figure 5C¨CG), but the apoptosis rate was significantly increased in SENEX silenced group (SS group).
--
--
--
--
p16-Rb
Activation
Western blot
We found that p16 ?and pRB expression levels were both significantly increased after the induction of doxorubicin, while RB ?expression level was decreased.
Human
L
apoptosis
33,015,970
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
HBP1
26959
protein coding
NP Cells
--
Intervertebral disc degeneration
Accelerate
RT-qPCR
The upregulation of HBP1 also af?fected collagen II expression and contributed to ?the rise of p16 expression.The ?HPB1 also triggered the IL-6, TNF, and MMP-3 ?expressions compared to the control. However, the silencing of HBP1 restrained the p16 expression and protected the collagen II level secreted by NP cells.
--
--
--
--
--
--
--
--
Human
L
apoptosis
32,964,956
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
BRD4
23476
protein coding
KYSE450
--
Oesophageal cancer
Prevent
SA--gal activity assay//Western blot
Treated with 125nM JQ1 for 6 days, the SA-¦Â-gal?positive cells significantly rose and increased subsequently in a ?dose-dependent manner.Immunoblotting also demonstrated that ?JQ1 increased p21 protein level within 6 days in KYSE450 cells.
AURKA//AURKB
Upregulation
Western blot//ChIP-Qpcr
Western blot analysis also showed that AURKA and AURKB protein were time- and ?dose-dependently decreased following JQ1 treatment. Data of ChIP-qPCR ?revealed that JQ1 suppressed BRD4 binding on the promoters of ?AURKA and AURKB genes in KYSE450 cells.
--
--
--
--
Human
L
apoptosis
32,954,665
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
MDM2
4193
protein coding
MCF-7
--
Breast ?cancer
Accelerate
SA--gal activity assay
We observed a significant increase in ¦Â- ?galactosidase staining in cells treated with the combination of 1¦ÌM NVP-CGM097 and 100 nM fulvestrant for ?72 h compared to vehicle treatment or treatment with ?either single agent alone (p < 0.01 vs NVP-CGM097; p < ?0.001 vs fulvestrant).
--
--
--
--
--
--
--
--
Human
HL
apoptosis
32,787,886
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
ASIC1
41
protein coding
NP-MSCs
--
Aging
Accelerate
CCK-8 assay//ELISA//Flow cytometry//SA--gal activity assay//Western blot
ASIC1 and ASIC3 were progressively upregulated in NP-MSCs derived from mild,moderate through to severely degenerated IVDs. CCK-8 showed that Pfirrmann grade II and grade IV isolates failed to grow at pH 6.6 in contrast to normal culture conditions.proliferative cells (S+G2/M phases) substantially declined from 25.72 to...
p53//p21//p27//Rb1//p16//MMP3//MMP9
Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation
Western blot
Exposure of isolated NP-MSCs to acidic growth conditions resulted in relatively increased levels of p53,p21,p27,Rb1 and p16 proteins.MMP3 and MMP9 levels also increased whereas aggrecan.
--
--
--
--
Human
L
cellular senescence
33,824,228
Gene
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
ASIC3
9311
protein coding
NP-MSCs
--
Aging
Accelerate
CCK-8 assay//ELISA//Flow cytometry//SA--gal activity assay//Western blot
ASIC1 and ASIC3 were progressively upregulated in NP-MSCs derived from mild,moderate through to severely degenerated IVDs. CCK-8 showed that Pfirrmann grade II and grade IV isolates failed to grow at pH 6.6 in contrast to normal culture conditions.proliferative cells (S+G2/M phases) substantially declined from 25.72 to...
p53//p21//p27//Rb1//p16//MMP3//MMP9
Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation//Upregulation
Western blot
Exposure of isolated NP-MSCs to acidic growth conditions resulted in relatively increased levels of p53,p21,p27,Rb1 and p16 proteins.MMP3 and MMP9 levels also increased whereas aggrecan.
--
--
--
--
Human
L
cellular senescence
33,824,228
Gene
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
LINC-PINT
378805
ncRNA
HCC,SPHC,SMMC-7721,MHCC-97H
--
Hepatocellular carcinoma
Accelerate
DNA FISH//Flow cytometry//IHC//SA--gal activity//Western blot
Our results confirmed that Ki67 was remarkably lower in the PINT87aa overexpression group.CircPINT less expressed in proliferating than senescent SMMC-7721 and MHCC-97H cells.CircPINT expression in proliferating and senescent SMMC-7721 and MHCC-97H cells.The proportion of G1 phase cells was increased in PINT87aa-overex...
FOXM1//PHB2
Downregulation//Downregulation
Co-IP//immunfluorescence experiments
PINT87aa could bind to the DNA-binding domain of FOXM.We observed co-localization of PINT87aa and FOXM1.
--
--
--
--
Human
L
cellular senescence
33,754,036
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
STING1
340061
protein coding
Chondrocytes
--
Osteoarthritis
Accelerate
SA--gal activity assay//Western blot
The results showed higher p16INK4a and p21 protein mea- sures in the STING-overexpressed and IL-1¦Â-treated chondrocytes. Although STING knockdown significantly reduced the IL-1¦Â-simulated upregulation of p16INK4a and p21 proteins, the knockdown of STING alone did not affect these proteins expression levels. We establ...
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--
--
--
NF-¦ÊB
Activation
Western blot//Immunofluorescence//SA-¦Â-gal activity assay//TUNEL assay
The results showed that higher phosphorylation of P65 and i¦Êb protein levels were seen in STING overexpressing and IL-1¦Â treated chondrocytes.The analysis of the immunofluorescence of nuclear P65 confirmed that STING activates NF-¦ÊB signaling.STING mediates the degradation of the ECM degradation through the NF-¦ÊBsi...
Human
L
apoptosis
33,414,452
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
EZH2
2146
protein coding
Chondrocytes
Human cartilage explants
Osteoarthritis
Accelerate
ELISA//RT-PCR//Safranin-O
We show that EPZ-6438 attenuated IL-1¦Â-induced expression and release of MMP-1, -3 and -13 in chondrocytes, suggesting that this inhibitor could reduce chondrocyte catabolism. We confirmed this hypothesis using human cartilage explants. Safranin-O staining in explants treated with IL-1¦Â for 48 h was less intense comp...
NGF
Upregulation
RT-PCR
We showed that EZH2 overexpression increases IL-1¦Â-mediated NGF expression. We showed that EZH2 overexpression increases IL-1¦Â-mediated NGF expression, while EPZ-6438 had the opposite effect and reduced IL-1¦Â-induced expression of NGF.
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--
--
--
Human
L
loss of proteostasis
33,177,650
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
MIR126
406913
ncRNA
DPSCs
--
Aging
Accelerate
MTT assay
For control group, data displayed that there was no any influence, while miR©\126 caused a reduced cell proliferative rate.For DPSCs at PD54, miR©\126 inhibition significantly increased the cell replication of DPSCs during 72 hours post©\transfection.
PTEN
Downregulation
qRT-PCR//Western blot
Here, the downregulation of PTEN was found in DPSC at PD54, compared with the DPSCs at PD16. Moreover, PTEN mRNA and protein level were also increased in senescent DPSCs transfected with miR©\126 inhibitor.
Akt
Activation
Western blot
The downstream Akt phosphorylation was remarkably upregulated in DPSCs at PD54, while transfection with miR©\126 inhibitor caused an impaired Akt phosphorylation in DPSCs.
Human
HL
apoptosis
33,150,661
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
NFKBIA
4792
protein coding
HDFs
--
Aging
Prevent
GO analysis//RNA-seq
The transcriptome of non©\irradiated NFKBIA©\depleted cells shared a strong overlap and the same GO terms with the senescent cells of the second phase.I¦ÊB¦Á rescue through ectopic overexpression of an NFKBIA mutant encoding the proteasome©\insensitive I¦ÊB¦ÁS32AS36A blocked the induction of the bona fide SASP factors.
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--
--
--
--
--
--
--
Human
HL
apoptosis
33,459,422
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
EZH2
2146
protein coding
HSCs,JS1,LX-2
--
Aging
Prevent
Flow cytometry//GO analysis//RT-qPCR//SA--gal activity assay//Western blot
Treatment of primary HSCs with DZNep, or transient transfection with potent siRNAs for Ezh2 silencing, resulted in more quiescent HSCs-phenotype and pronounced growth retardation, remarkably weakened H3K27me2/3, and significantly downregulated ¦Á-SMA and COL1A.EZH2 inhibition by DZNep in mouse JS1 cells resulted in cel...
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--
--
--
TGF-¦Â-SMAD
Downregulation
RNA-seq
154 out of the 351 associated DEGs in knowledgebase have measurement direction consistent with Tgf¦Â1 inhibition (P = 9.96E-30, Z-score = -2.087), the majority (127) of which are downregulated activator or effector genes, while a few (27) are upregulated inhibitor genes.
Human
HL
apoptosis
33,391,480
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
KDM6B
23135
protein coding
HSCs,JS1
--
Aging
Accelerate
ChIP-qPCR//RT-qPCR//Western blot
Treatment of primary HSCs with GSK-J4, an jumonji H3K27me3 demethylase inhibitor of JMJD3 30, resulted in enhanced cell growth, morphological transition from quiescent HSCs to myofibroblast, reinforced H3K27me3, and upregulated fibrotic markers.DZNep-mediated EZH2 inhibition and adenovirus-mediated Jmjd3 overexpression...
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--
--
--
--
--
--
--
Human
HL
apoptosis
33,391,480
Gene
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0