Circ5379-6, a circular form of tumor suppressor PPAR?±, participates in the inhibition of hepatocellular carcinoma tumorigenesis and metastasis

摘要

This study aimed to investigate the role of circRNAs encoded by PPARα in regulating the pathogenesis processes of hepatocellular carcinoma (HCC). Comprehensive analysis of 3 circular RNA databases revealed multiple circular RNAs within the PPARα gene. The candidate circRNAs were first structurally validated via specific convergent and divergent primer amplification, RNase R treatment, and Sanger sequencing. According to a further validation of the cell viability assay, cell cycle and apoptosis, and transwell assays, the circRNAs correlated to PPARα were obtained. Their functions in tumorigenesis were further validated via the subcutaneous tumor model and the migration model in nude mice. We showed that the overexpression of circ5379-6 decreased cell proliferation, inhibited cell migration and invasion, and induced cell apoptosis in the HCC cell lines. Consistently, in vivo studies in nude mice confirmed that the overexpression of circ5379-6 effectively inhibited the tumorigenesis and metastasis of HCC. We conclude that circ5379-6 plays a role similar to its linear counterpart PPARα to inhibit HCC tumorigenesis and progression.