Background: Hepatocellular carcinoma (HCC) has ranked sixth most common cancer in number of malignancies in the worldwide. There is plenty of evidence indicated that circular RNAs (circRNAs) exert vitally important roles in the progression of many malignancies. Nevertheless, the molecular mechanism and role of hsa_circ_0006421 in HCC are still unclear. The aim of our research is to verify the molecular mechanism and effects of hsa_circ_0006421 in HCC.
Methods: First, we collected 34 paired HCC tissues and paraneoplastic tissues surgically resected from patients and analyzed the expression of hsa_circ_0006421 in HCC tissues and its relationship with clinicopathological characteristics. Then, CCK8, colony formation, cell migration assay, transwell invasion assay and Annexin-V/PI staining were used to assess the effects of hsa_circ_0006421 on the growth, migration, invasion and apoptosis of HCC cells. Next, quantitative real-time PCR (qRT-PCR) and Western blots were used to detect the expression of miR-134-5p, CELF2 and hsa_circ_0006421. In the end, the targeting interactions of miR-134-5p and hsa_circ_0006421，CELF2 and miR-134-5p were explored by the dual-luciferase reporter assay.
Results: Hsa_circ_0006421 was diminished in HCC tissues and its down-regulation was related to cirrhosis history. Knocking down hsa_circ_0006421 promoted HCC cells growth, migration, invasion and inhibited apoptosis, whereas overexpressing hsa_circ_0006421 had the opposite effects. Moreover, hsa_circ_0006421 served as the competing endogenous RNA of miR-134-5p. Subsequently, there was a reciprocal relationship between CELF2 and miR-134-5p. Hsa_circ_0006421 could positively regulate the protein level of CELF2 in HCC.
Conclusion: hsa_circ_0006421 inhibits liver cancer by regulating miR-134-5p/CELF2 axis.