Ma Hongxi, Huang Chunchun, Huang Qiuhuan, Li Guangzhi, Li Jun, Huang Bin, Zhong Qiuhong, Cao Cong
Clinical Laboratory, Wuzhou Gongren Hospital, Wuzhou, China.
Department of General Practice, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Front Oncol. 2021 Jan 27;10:592884. doi: 10.3389/fonc.2020.592884. eCollection 2020.
Recent studies have reported a close association between circRNAs and cancer development. CircRNAs have been recognized to be involved in various biological processes. Up to now, the function of circRNAs in hepatocellular carcinoma (HCC) is still poorly known. qRT-PCR was used to test circ_0014717 expression in HCC tissue samples and cells was determined. It was shown that circ_0014717 was significantly decreased in HCC. Then, we observed overexpression of circ_0014717 obviously repressed HCC cell growth, migration and invasion. Next, we predicted circ_0014717 acted as a sponge of miR-668-3p. miR-668-3p has been reported to participate in several diseases. In our work, it was shown miR-668-3p was greatly increased in HCC and the direct binding sites between circ_0014717 and miR-668-3p were validated. In addition, B-cell translocation gene 2 (BTG2) is closely involved in cellular carcinogenic processes. BTG2 was predicted as a target for miR-668-3p. By performing rescue assays, we demonstrated that circ_0014717 repressed HCC progression inhibiting BTG2 expression and sponging miR-668-3p. It was manifested loss of circ_0014717 induced HCC progression, which was reversed by BTG2 in Hep3B cells. In conclusion, our findings illustrated a novel circ_0014717/miR-668-3p/BTG2 regulatory signaling pathway in HCC.
近期研究报道了环状RNA(circRNAs)与癌症发展之间存在密切关联。circRNAs已被认为参与多种生物学过程。到目前为止,circRNAs在肝细胞癌(HCC)中的功能仍知之甚少。采用qRT-PCR检测HCC组织样本中circ_0014717的表达,并测定细胞中的表达情况。结果显示,circ_0014717在HCC中显著降低。然后,我们观察到circ_0014717的过表达明显抑制了HCC细胞的生长、迁移和侵袭。接下来,我们预测circ_0014717作为miR-668-3p的海绵。据报道,miR-668-3p参与多种疾病。在我们的研究中,结果显示miR-668-3p在HCC中显著上调,并且验证了circ_0014717与miR-668-3p之间的直接结合位点。此外,B细胞易位基因2(BTG2)密切参与细胞致癌过程。BTG2被预测为miR-668-3p的靶标。通过进行挽救实验,我们证明circ_0014717通过抑制BTG2表达和吸附miR-668-3p来抑制HCC进展。结果表明,circ_0014717的缺失诱导了HCC进展,但在Hep3B细胞中被BTG2逆转。总之,我们的研究结果阐明了HCC中一种新的circ_0014717/miR-668-3p/BTG2调控信号通路。