Circ-TCF4.85 silencing inhibits cancer progression through microRNA-486-5p-targeted inhibition of ABCF2 in hepatocellular carcinoma.

Jun Gao,Fan Zhou,Xiang‐Bao Yin,Xin Yu,Chao Dai

doi:10.1002/1878-0261.12603

Abstract

The current study aimed to explore the role of the circular RNA circ‐TCF4.85 and its downstream target microRNA‐486‐5p (miR‐486‐5p) in hepatocellular carcinoma (HCC) development. Circ‐TCF4.85 was detected to be highly expressed in HCC tissues. Next, we found that silencing of circ‐TCF4.85 repressed HCC cell proliferation, invasion, and migration, while enhancing apoptosis. In addition, biotin‐coupled probe pull‐down and miRNA capture assays, as well as fluorescence in situ hybridization, confirmed that circ‐TCF4.85 could bind to miR‐486‐5p. In rescue experiments, miR‐486‐5p had the potential to eliminate the tumor‐suppressive effects of circ‐TCF4.85 knockdown in HCC. Moreover, miR‐486‐5p was shown to target ABCF2 gene, which was positively regulated by circ‐TCF4.85. Finally, nude mice subcutaneously injected with si‐circ‐TCF4.85‐transfected HCC cells presented with inhibited xenograft tumor formation in vivo. Taken together, our results reveal that silencing of circ‐TCF4.85 suppresses HCC progression via miR‐486‐5p‐targeted inhibition of ABCF2.

Highlights

Hepatocellular carcinoma (HCC) is the 5th most frequently occurring cancer and the most ubiquitous liver malignancy throughout the world, with rising incidence and mortality rates (Mittal and El-Serag, 2013; Tao et al, 2011)
We adopted the CircNet website to further speculate on the possible regulation mechanisms of circ-TCF4.85 (Fig. 1B) and applied the the Cancer Genome Atlas (TCGA) database to analyze the potential regulatory genes, which demonstrated that ATP-binding cassette subfamily F member 2 (ABCF2) was highly expressed in hepatocellular carcinoma (HCC) and shared a correlation with HCC prognosis (Fig. 1C,D)
We recorded the clinicopathological characteristics of 46 patients including gender, age, hepatitis B virus (HBV) infection, tumor size, vascular invasion, distant metastasis, and clinical staging

Summary

Introduction

Hepatocellular carcinoma (HCC) is the 5th most frequently occurring cancer and the most ubiquitous liver malignancy throughout the world, with rising incidence and mortality rates (Mittal and El-Serag, 2013; Tao et al, 2011). Several noncoding RNA (ncRNA), such as long ncRNA and microRNA (miRNA or miR), have been identified as potential targets for HCC therapies (Li et al, 2017; Abbreviations ABC, ATP-binding cassette; ABCF2, ATP-binding cassette subfamily F member 2; AFP, a-fetoprotein; ANOVA, analysis of variance; circRNA, circular RNA; DAPI, 4’,6-diamidino-2-phenylindole; DMEM, Dulbecco’s modified Eagle’s medium; FISH, fluorescence in situ hybridization; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; L, length; miRNA or miR, microRNA; MUT, mutant; ncRNA, noncoding RNA; PIK3R1, phosphoinositide-3-kinase, regulatory subunit 1 (alpha); ROC, receiver operating characteristic; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; TBST, Tris-buffered saline Tween-20; TCGA, The Cancer Genome Atlas; V, volume; W, width; WT, wild-type

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