• J. Cell. Mol. Med. · Feb 2020

    hsa_circ_0000092 promotes hepatocellular carcinoma progression through up-regulating HN1 expression by binding to microRNA-338-3p.

    • Jian Pu, Jianchu Wang, Wenchuan Li, Yuan Lu, Xianjian Wu, Xidai Long, Chunying Luo, and Huamei Wei.
    • Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
    • J. Cell. Mol. Med. 2020 Feb 20.

    AbstractCircular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR-338-3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR-338-3p and HN1 was determined by dual-luciferase reporter, RNA pull-down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR-338-3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR-338-3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR-338-3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR-338-3p to up-regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR-338-3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down-regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR-338-3p-mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC.© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

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