Long noncoding RNA TP53TG1 suppresses the growth and metastasis of hepatocellular carcinoma by regulating the PRDX4/β-catenin pathway

Emerging evidence has shown that aberrant expression of lncRNA-TP53TG1 plays important roles in various malignancies. However, the biological functions of lncRNA-TP53TG1 in hepatocarcinogenesis, as well as the underlying mechanisms, remain largely unknown. Here, we assessed whether lncRNA-TP53TG1 plays a key role in the progression of hepatocellular carcinoma (HCC). The expression of lncRNA-TP53TG1 was significantly decreased in HCC tissues and cells. Decreased expression of lncRNA-TP53TG1 was associated with aggressive clinical phenotypes and a poor prognosis. Ectopic expression of lncRNA-TP53TG1 inhibited hepatoma cell proliferation and migration in vitro and in vivo, whereas lncRNA-TP53TG1 knockdown exerted the opposite effects. Furthermore, lncRNA-TP53TG1 played an important role in slowing the epithelial-mesenchymal transition (EMT) process in HCC. Mechanistically, lncRNA-TP53TG1 physically interacted with PRDX4 and promoted its ubiquitin-mediated degradation, resulting in the inactivation of the WNT/beta-catenin signaling pathway in hepatoma cells. Our findings demonstrate a novel mechanism by which lncRNA-TP53TG1 exerts its tumor-suppressive effects through the WNT/beta-catenin signaling pathway in a PRDX4-mediated manner in HCC. Based on these results, lncRNA-TP53TG1 potentially represents a prognostic indicator and therapeutic target for patients with HCC.

Automated summary

The study revealed that lncRNA-TP53TG1 is downregulated in hepatocellular carcinoma (HCC) and exerts its tumor-suppressive effects by physically interacting with PRDX4 to promote its ubiquitin-mediated degradation, thus inhibiting the WNT/beta-catenin signaling pathway in HCC.