circELMOD3 increases and stabilizes TRIM13 by sponging miR-6864-5p and direct binding to inhibit HCC progression

Abstract

Many circular RNAs (circRNAs) have been identified to be associated with hepatocellular carcinoma (HCC) progression. We aim to explore the diagnostic potential, functions, and mechanism of circELMOD3 in HCC. Differentially expressed circRNAs in HCC and its paired adjacent tissues were identified by RNA sequencing. circELMOD3 was downregulated in HCC tissues and was related to clinicopathological characteristics of HCC patients. Additionally, plasma circELMOD3 was shown to be a highly sensitive and non-invasive biomarker to distinguish HCC from healthy controls. Functional assays showed that circELMOD3 inhibited proliferation and induced apoptosis of HCC cells both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, RNA antisense purification (RAP) and luciferase reporter assays verified that circELMOD3 functioned as a sponge for miR-6864-5p leading to increased expression of its target gene <i>TRIM13</i>. Interestingly, RNA stability test demonstrated that circELMOD3 overexpression led to enhanced stability of its directly bound <i>TRIM13</i> mRNA, which in turn co-activated the p53 signaling pathway.