Hsa_circ_0103809 promotes cell proliferation and inhibits apoptosis in hepatocellular carcinoma by targeting miR-490-5p/SOX2 signaling pathway

Am J Transl Res. 2018 Jun 15;10(6):1690-1702. eCollection 2018.

Abstract

Background: Circular RNAs (circRNAs) represent a class of non-coding RNAs that are emerging as important regulators during tumorigenesis and provide potential targets for cancer intervention. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) have not been completely clarified. Herein, the role of hsa_circ_0103809 was investigated in HCC tissues and cell lines.

Methods: High-throughput circRNA sequencing was performed to detect the expression profiles of circRNA in HCC tissues. The CCK-8, wound healing and flow cytometry were performed to measure the cell viability, migration and apoptosis in HCC cells. The expression levels of gene and protein in HCC tissues and cell lines were assayed by RT-qPCR and western blotting, respectively. Immunohistochemical staining was used to assess the protein expression of SOX2 in HCC tissues.

Results: We discovered that hsa_circ_0103809 was significantly increased in HCC tissues and cell lines. Knockdown of hsa_circ_0103809 inhibited proliferation and migration and induced apoptosis in HCC cell lines. Investigation to the molecular mechanisms of hsa_circ_0103809 in HCC cells had revealed that hsa_circ_0103809 directly suppressed miR-490-5p, which targeted to the 3'-UTR of SOX2. Hsa_circ_0103809 loss-of-function could increase the expression of miR-490-5p as well as decreased the expression of SOX2. Furthermore, we found that si-0103809 induced growth and migration inhibition and apoptosis could be reversed by transfected with miR-490-5p inhibitors or SOX2 in HCC cells.

Conclusion: Our findings suggested that hsa_circ_0103809 might facilitate HCC malignant progression, at least partially, by regulating miR-490-5p/SOX2 signaling pathway.

Keywords: Hepatocellular carcinoma; SOX2; circRNA; hsa_circ_0103809; miR-490-5p.