TM6SF2 overexpression suppresses the proliferation and promotes apoptosis of human hepatocellular carcinoma cells.

Transmembrane protein 6 superfamily member 2 (TM6SF2) is a potential tumor suppressor in hepatocellular carcinoma (HCC). At present, the role of TM6SF2 in HCC is poorly studied. The aim of the present study was to elucidate the potential role of TM6SF2 in hepatocellular carcinoma and its associated molecular mechanisms. The correlation between TM6SF2 and HCC progression was assessed using a bioinformatics approach. A TM6SF2‑overexpressing Huh‑7 cell model was constructed to examine the effects of TM6SF2 on cell proliferation, migration, invasion, cell‑cycle distribution, and apoptosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) in the control Vector and TM6SF2 groups were performed using RNA sequencing (RNA‑Seq) data. Reverse transcription‑quantitative PCR and western blotting were used to verify the expression of candidate DEGs involved in cell cycle regulation and apoptosis. Overexpression of TM6SF2 inhibited HCC cell proliferation, invasion, and migration and promoted apoptosis. TM6SF2 overexpression induced S‑phase cell‑cycle arrest and promoted apoptosis in Huh‑7 cells. RNA‑Seq analysis showed that the majority of DEGs were involved in cell growth and biological processes, including the negative regulation of cell growth. KEGG pathway analysis identified the p53 signaling pathway as significantly enriched. Western blot analysis further showed increased levels of phosphorylated p53 and p21, suggesting p53‑related molecular changes. These findings suggest that TM6SF2 may exert anti‑tumor effects in Huh‑7 cells by inducing S‑phase cell‑cycle arrest and promoting apoptosis. The observed increases in phosphorylated p53 and p21 indicate that p53‑related molecular changes may be associated with TM6SF2 overexpression, although this requires further validation.