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.

Our findings suggest that miR-204 plays a protective role by inhibiting thyroid cancer cell proliferation, and may identify new targets for anti-cancer treatment.

Background/aimIncreasing evidence show microRNAs (miRNAs) are engaged in hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of miR-144 in HCC, as well as to identify its underlying mechanism.MethodsThe expression levels of miR-144 were assessed in multiple HCC cell lines, as well as in liver tissues from patients with HCC. We further examined the effects of miR-144 on HCC. The molecular target of miR-144 was identified using a computer algorithm and confirmed experimentally.ResultsWe found that the levels of miR-144 were frequently downregulated in human HCC tissues and cell lines, and overexpression of miR-144 dramatically inhibited HCC metastasis, invasion, cell cycle, epithelial–mesenchymal transition, and chemoresistance. We further verified the SMAD4 as a novel and direct target of miR-144 in HCCs.ConclusionTaken together, overexpression of miR-144 or downregulation of SMAD4 may prove beneficial as therapeutic strategies for HCC treatment.