Circular RNA circ_0014717 Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating miR-668-3p/BTG2 Axis.

Hongxi Ma,Jun Li,Qiuhong Zhong,Bin Huang,Qiuhuan Huang,Cong Cao,Chunchun Huang,Guangzhi Li

doi:10.3389/fonc.2020.592884

Abstract

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 via 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.

Highlights

Hepatocellular carcinoma (HCC) is becoming a prevalent cancer across the world [1, 2]
CircTP63 can act as a ceRNA to induce lung cancer progression via inducing FOXM1 [11]
We demonstrated the mRNA levels of top six predicted genes after the up-regulation of miR-668-3p in Hep3B and SMMC7721 cells in Figures 5A, B via consulting online bioinformatics analysis. miR-6683p overexpression depressed the expression of B-cell translocation gene 2 (BTG2) in hepatocellular carcinoma (HCC) cells most significantly

Summary

INTRODUCTION

Hepatocellular carcinoma (HCC) is becoming a prevalent cancer across the world [1, 2]. In China, HCC contribute a lot to a number of cancer-related death every year [3]. CircRNAs may exhibit specific biological functions and they are significant mediators in tumors through various mechanisms [8,9,10]. CircRNA_5692 represses the progression of HCC via sponging miR-328-5p to induce DAB2IP level [13]. In colorectal cancer, circ_0014717 can exhibit tumor-suppressive roles [15]. The detail role of circ_0014717 in HCC development is barely known. We hypothesized down-regulated circ_0014717 expression may act as a promising biomarker for HCC via regulating miR-668-3p and BTG2

MATERIALS AND METHODS

RESULTS

DISCUSSION

Findings

ETHICS STATEMENT