Circ-ZEB1.33 promotes the proliferation of human HCC by sponging miR-200a-3p and upregulating CDK6

Yuhua Gong,Xuemei Wang,Rong Song,Long Li,Liang Zhu,Di Wu,Jinzhong Mao

doi:10.1186/s12935-018-0602-3

Abstract

BackgroundAccumulating data indicated that circRNA plays important roles in regulating many biological processes of the tumor, the present study is designated for exploring roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis in human hepatocellular carcinoma (HCC).MethodsThe regulation axis as predicted by using online tool circNet, the expression and correlation of circ-ZEB1.33-miR-200a-3p-CDK6 was verified in human HCC. The diagnostic value of both tumor and serum circ-ZEB1.33 was estimated by using clinical samples. The roles of circ-ZEB1.33-miR-200a-3p-CDK6 in regulating cell cycle were explored by using in vitro studies.ResultsOverexpression of circ-ZEB1.33 and CDK6, downregulation of miR-200a-3p were detected in human HCC tissues, negative correlation between circ-ZEB1.33 and miR-200a-3p, positive correlation between circ-ZEB1.33 and CDK6 were confirmed in human HCC tissues. Tissue and serum circ-ZEB1.33 were related to different TMN stages and prognosis in HCC patients. RNA pull-down assay implied that circ-ZEB1.33 could decrease miR-200a-3p by sponging miR-200a-3p, and the luciferase reporter assay indicated that miR-200a-3p could downregulate CDK6 transcription by targeting its 3′UTR. The in vitro assays indicated that circ-ZEB1.33 could promote the proliferation of HCC cells by increasing the percentage of S phase regulated by CDK6/Rb.ConclusionProliferation promotion roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis are existed and verified in human HCC, both tumor and serum circ-ZEB1.33 can serve as an indicator for the prognosis of HCC patients.

Highlights

Accumulating data indicated that circRNA plays important roles in regulating many biological processes of the tumor, the present study is designated for exploring roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis in human hepatocellular carcinoma (HCC)
Overexpression of Circ‐ZEB1.33 in human tumor tissues and serum in HCC patients We queried the possible interaction between circZEB1.33 and sponge miRNA by using online prediction tool, CircNet, we found that circ-ZEB1.33 might promote CDK6 expression by sponge miR-140-3p and miR-200a-3p (Fig. 1a)
The results indicated that the serum level of circ-ZEB1.33 was significantly higher in HCC patients compared to the healthy control (Fig. 1e)

Summary

Introduction

Accumulating data indicated that circRNA plays important roles in regulating many biological processes of the tumor, the present study is designated for exploring roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis in human hepatocellular carcinoma (HCC). CircRNAs are mostly non-translated, can occur in any genomic region including gene-bearing regions and intergenic regions, and range in length from few hundred to thousands of nucleotides [3]. CircRNAs are resistant to exonuclease-mediated degradation due to their characters in the absence of 5′ or 3′ ends. Serum circRNA can be detected in the peripheral serum, and make them ideal biomarkers for disease diagnosis or prediction [1]. Increasing amount of related research has been published addressing the diagnosis value of circRNA in the diseases including hypertension, lupus nephritis, diabetic retinopathy as well as liver cancer

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Discussion

Conclusion