Sohlh2 Promotes the Progression of Hepatocellular Carcinoma via TGM2‐Mediated Autophagy

ABSTRACT Liver cancer is the third leading cause of cancer‐related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for 85% of liver cancer‐related deaths. Autophagy controls HCC cell growth, invasion, metastasis, drug resistance, and stemness. Spermatogenesis and oogenesis basic helix‐loop‐helix transcription factor 2 (Sohlh2) can bind to the E‐boxes in the promoter regions of target genes, which are involved in multiple neoplasms. In this study, Sohlh2 was highly expressed in HCC tissues and was related to poor prognosis. Moreover, Sohlh2 overexpression promoted the proliferation, migration, invasion, and metastasis of HCC cells in vivo and in vitro. However, Sohlh2 silencing inhibited proliferation, migration, invasion, and metastasis of HCC cells in vivo and in vitro. Mechanistically, Sohlh2 could bind to the promoter of TGM2 and enhance its transcriptional activity, thereby enhancing the autophagy of HCC cells. Furthermore, Sohlh2 protein levels were positively associated with TGM2 expression in HCC tissues. Taken together, these results demonstrate that Sohlh2 can promote HCC progression via TGM2‐mediated autophagy, implying that Sohlh2 is a promising candidate for HCC treatment.