HDAC1-induced epigenetic silencing of ASPP2 promotes cell motility, tumour growth and drug resistance in renal cell carcinoma

Li, Huayi; Wang, Xingwen; Zhang, Cheng; Cheng, Yiwei; Wang, Yuanlin; Zhao, Kunming; Ge, Wenjie; Cai, Anyong; Zhang, Yao; Han, Fengtong; Hu, Ying

doi:10.1016/j.canlet.2018.06.009

Cited by 15 publications

(17 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A growing volume of evidence has suggested the incorporation of HDACs in the development of renal tumors, illustrating its decrease or suppression as a prospective therapeutic method to restrain renal tumors (49,50). Recent studies suggest that vorinostat possesses antitumor activity against soft tissue sarcomas, gastric and lung cancer, and even RCC (51–54). In addition, the anti-virus effect of vorinostat in patients with HIV is also reported (55–57).…”

Section: Discussionmentioning

confidence: 99%

The underlying molecular mechanism and potential drugs for treatment in papillary renal cell carcinoma: A study based on TCGA and Cmap datasets

Pang

Lin

et al. 2019

Oncol Rep

View full text Add to dashboard Cite

Papillary renal cell carcinoma (PRCC) accounts for 15–20% of all kidney neoplasms and continually attracts attention due to the increase in the incidents in which it occurs. The molecular mechanism of PRCC remains unclear and the efficacy of drugs that treat PRCC lacks sufficient evidence in clinical trials. Therefore, it is necessary to investigate the underlying mechanism in the development of PRCC and identify additional potential anti-PRCC drugs for its treatment. The differently expressed genes (DEGs) of PRCC were identified, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for functional annotation. Then, potential drugs for PRCC treatment were predicted by Connectivity Map (Cmap) based on DEGs. Furthermore, the latent function of query drugs in PRCC was explored by integrating drug-target, drug-pathway and drug-protein interactions. In total, 627 genes were screened as DEGs, and these DEGs were annotated using KEGG pathway analyses and were clearly associated with the complement and coagulation cascades, amongst others. Then, 60 candidate drugs, as predicted based on DEGs, were obtained from the Cmap database. Vorinostat was considered as the most promising drug for detailed discussion. Following protein-protein interaction (PPI) analysis and molecular docking, vorinostat was observed to interact with C3 and ANXN1 proteins, which are the upregulated hub genes and may serve as oncologic therapeutic targets in PRCC. Among the top 20 metabolic pathways, several significant pathways, such as complement and coagulation cascades and cell adhesion molecules, may greatly contribute to the development and progression of PRCC. Following the performance of the PPI network and molecular docking tests, vorinostat exhibited a considerable and promising application in PRCC treatment by targeting C3 and ANXN1.

show abstract

Section: Discussionmentioning

confidence: 99%

The underlying molecular mechanism and potential drugs for treatment in papillary renal cell carcinoma: A study based on TCGA and Cmap datasets

Pang

Lin

et al. 2019

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…ASPP2 was inhibited by histone deacetylatlase 1, which acted by preventing the binding between transcription factor (E2F1) and the ASPP2 promoter. 11 To explore the role of ASPP2 in the progression of AKI, we prepared an AKI mouse model (Figure 3). Therefore, ASPP2 deficiency exerts a renoprotective effect on AKI.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of apoptosis‐stimulating protein two of p53 ameliorates acute kidney injury induced by ischemia reperfusion in mice through upregulation of autophagy

Zhou

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Acute kidney injury (AKI) has become a common disorder with a high risk of morbidity and mortality, which remains major medical problem without reliable and effective therapeutic intervention. Apoptosis‐stimulating protein two of p53 (ASPP2) is a proapoptotic member that belongs to p53 binding protein family, which plays a key role in regulating apoptosis and cell growth. However, the role of ASPP2 in AKI has not been reported. To explore the role of ASPP2 in the progression of AKI, we prepared an AKI mouse model induced by ischaemia reperfusion (I/R) in wild‐type (ASPP2 +/+ ) mice and ASPP2 haploinsufficient (ASPP2 +/− ) mice. The expression profile of ASPP2 were examined in wild‐type mice. The renal injury, inflammation response, cellular apoptosis and autophagic pathway was assessed in ASPP2 +/+ and ASPP2 +/− mice. The renal injury, inflammation response and cellular apoptosis was analysed in ASPP2 +/+ and ASPP2 +/− mice treated with 3‐methyladenine or vehicle. The expression profile of ASPP2 showed an increase at the early stage while a decrease at the late stage during renal injury. Compared with ASPP2 +/+ mice, ASPP2 deficiency protected mice against renal injury induced by I/R, which mainly exhibited in slighter histologic changes, lower levels of blood urea nitrogen and serum creatinine, and less apoptosis as well as inflammatory response. Furthermore, ASPP2 deficiency enhanced autophagic activity reflecting in the light chain 3‐II conversion and p62 degradation, while the inhibition of autophagy reversed the protective effect of ASPP2 deficiency on AKI. These data suggest that downregulation of ASPP2 can ameliorate AKI induced by I/R through activating autophagy, which may provide a novel therapeutic strage for AKI.

show abstract

“…Recently, it has been reported that vorinostat inhibits cell proliferation, invasion and drug resistance in renal cell carcinoma, follicular lymphoma, and glioblastoma. [23][24][25] These findings strongly suggested that melatonin and a HDAC inhibitor might have synergistic therapeutic effects in GBMs and GSCs. 16,26 Glioblastoma cells have been reported to be resistant to apoptosis during chemotherapy of GBM patients.…”

Section: Introductionmentioning

confidence: 85%

“…Therefore, vorinostat is used to improve the therapeutic effect of various carcinomas. Recently, it has been reported that vorinostat inhibits cell proliferation, invasion and drug resistance in renal cell carcinoma, follicular lymphoma, and glioblastoma . These findings strongly suggested that melatonin and a HDAC inhibitor might have synergistic therapeutic effects in GBMs and GSCs …”

Section: Introductionmentioning

confidence: 95%

Inhibition of TFEB oligomerization by co‐treatment of melatonin with vorinostat promotes the therapeutic sensitivity in glioblastoma and glioma stem cells

Sung

Kim

Kwak

et al. 2019

Journal of Pineal Research

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most aggressive malignant glioma and most lethal form of human brain cancer (Clin J Oncol Nurs. 2016;20:S2). GBM is also one of the most expensive and difficult cancers to treat by the surgical resection, local radiotherapy, and temozolomide (TMZ) and still remains an incurable disease. Oncomine platform analysis and Gene Expression Profiling Interactive Analysis (GEPIA) show that the expression of transcription factor EB (TFEB) was significantly increased in GBMs and in GBM patients above stage IV. TFEB requires the oligomerization and localization to regulate transcription in the nucleus. Also, the expression and oligomerization of TFEB proteins contribute to the resistance of GBM cells to conventional chemotherapeutic agents such as TMZ. Thus, we investigated whether the combination of vorinostat and melatonin could overcome the effects of TFEB and induce apoptosis in GBM cells and glioma cancer stem cells (GSCs). The downregulation of TFEB and oligomerization by vorinostat and melatonin increased the expression of apoptosis‐related genes and activated the apoptotic cell death process. Significantly, the inhibition of TFEB expression dramatically decreased GSC tumor‐sphere formation and size. The inhibitory effect of co‐treatment resulted in decreased proliferation of GSCs and induced the expression of cleaved PARP and p‐γH2AX. Taken together, our results definitely demonstrate that TFEB expression contributes to enhanced resistance of GBMs to chemotherapy and that vorinostat‐ and melatonin‐activated apoptosis signaling in GBM cells by inhibiting TFEB expression and oligomerization, suggesting that co‐treatment of vorinostat and melatonin may be an effective therapeutic strategy for human brain cancers.

show abstract

HDAC1-induced epigenetic silencing of ASPP2 promotes cell motility, tumour growth and drug resistance in renal cell carcinoma

Cited by 15 publications

References 42 publications

The underlying molecular mechanism and potential drugs for treatment in papillary renal cell carcinoma: A study based on TCGA and Cmap datasets

The underlying molecular mechanism and potential drugs for treatment in papillary renal cell carcinoma: A study based on TCGA and Cmap datasets

Deficiency of apoptosis‐stimulating protein two of p53 ameliorates acute kidney injury induced by ischemia reperfusion in mice through upregulation of autophagy

Inhibition of TFEB oligomerization by co‐treatment of melatonin with vorinostat promotes the therapeutic sensitivity in glioblastoma and glioma stem cells

Contact Info

Product

Resources

About