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SIRT5 promotes cell proliferation and invasion in hepatocellular carcinoma by targeting E2F1
Liang Chang1, Liang Xi2, Yubin Liu3
1Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Abstract:
Sirtuin 5 (SIRT5) is a member of the NAD+‑dependent class III protein deacetylases. Although it is known that SIRT5 deacetylates and activates urate oxidase in the liver mitochondria of mice, the mechanism of SIRT5 in the proliferation of hepatocellular carcinoma (HCC) remains to be fully elucidated. The present study investigated the expression and functional significance of SIRT5 in HCC, and examined the relevant mechanism. SIRT5 was found to be upregulated in HCC tissues and cell lines, and the higher expression of SIRT5 indicated poorer overall survival. Reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis, chromatin immunoprecipitation analysis, and luciferase reporter gene, proliferation and Transwell assays were performed to elucidate the function of SIRT5 in the regulation of cell proliferation and invasion in human HCC. Functionally, it was observed that the inhibition of SIRT5 significantly suppressed HCC cell proliferation and invasion, whereas the overexpression of SIRT5 promoted HCC cell proliferation and invasion in vitro. E2F transcription factor 1 (E2F1) was identified as a novel target gene of SIRT5. In addition, the knockdown of SIRT5 induced the expression of E2F1, and the knockdown of E2F1 in HCC cells partially reversed the effect of SIRT5 in promoting cell proliferation and invasion. Collectively, these data provide the first evidence, to the best of our knowledge, that the SIRT5 gene has an important regulatory role in liver carcinogenesis, and may function as a novel potential therapeutic target for HCC.
Insights
Sirtuin 5 (SIRT5) is upregulated in hepatocellular carcinoma (HCC), promoting cancer cell proliferation and invasion. Inhibiting SIRT5 may offer a new therapeutic strategy for liver cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Sirtuin 5 (SIRT5) is an NAD+-dependent deacetylase involved in liver metabolism.
- Its precise role in hepatocellular carcinoma (HCC) proliferation is not fully understood.
Purpose of the Study:
- To investigate the expression and function of SIRT5 in HCC.
- To elucidate the mechanism by which SIRT5 influences HCC progression.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis for expression.
- Chromatin immunoprecipitation (ChIP) and luciferase reporter assays for mechanism.
- In vitro proliferation and Transwell assays for functional analysis.
Main Results:
- SIRT5 was upregulated in HCC tissues and cell lines, correlating with poorer survival.
- SIRT5 inhibition suppressed HCC cell proliferation and invasion; overexpression promoted them.
- E2F transcription factor 1 (E2F1) was identified as a novel SIRT5 target, mediating its effects on proliferation and invasion.
Conclusions:
- SIRT5 plays a significant role in promoting HCC cell proliferation and invasion.
- SIRT5 acts via regulating E2F1 expression.
- SIRT5 represents a potential therapeutic target for HCC.
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