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Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation

Authors Yang G, Zhang T, Ye J, Yang J, Chen C, Cai S, Ma J

Received 27 January 2019

Accepted for publication 15 June 2019

Published 12 July 2019 Volume 2019:11 Pages 6499—6509

DOI https://doi.org/10.2147/CMAR.S203137

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eskazan


Guangpu Yang, Tianhao Zhang, Jinning Ye, Jie Yang, Chuangqi Chen, Shirong Cai, Jinping Ma

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People’s Republic of China

Background: As a class of endogenous noncoding RNAs, some circular RNAs (circRNAs) have recently been reported to play a role in the regulation of tumorigenesis and progression in colorectal cancer (CRC). However, the mechanisms by which most these circRNAs function in CRC are still unclear.
Purpose: The objective of this study was to identify the role of circRNA-ITGA7 in CRC cell proliferation.
Patients and methods: Human genome-wide circRNA microarray v2 analysis was used for expression profile analysis. Target genes were predicted using online bioinformatics database, including TargetScan, miRDB, miRTarbase and miRMap. Gene overexpression and silencing cell models were built using cell transfection. qRT-PCR and Western blot were performed for gene and protein expression assessment. CCK8, colony formation and cell cycle analysis were used for proliferation testing. Annexin V-FITC analysis was performed for apoptosis detection.
Results: CircRNA sequencing analysis suggested that compared to that in adjacent normal control tissue, the expression of circ-ITGA7, a novel circRNA, is decreased significantly in CRC. Gain-of-function studies further demonstrated that circ-ITGA7 suppressed proliferation of CRC cells. Based on prediction and verification, we subsequently revealed that miR-3187-3p is a circ-ITGA7-associated miRNA. Furthermore, RNA sequencing and bioinformatics analyses showed that ASXL1-5ʹUTR, the target of miR-3187-3p, is upregulated in circ-ITGA7-overexpressed cells and mediates the circ-ITGA7-induced suppression of proliferation.
Conclusion: Circ-ITGA7 might suppress CRC proliferation by sponging miR-3187-3p and increasing ASXL1 expression. Thus, circ-ITGA7 might be a potential diagnostic biomarker and a therapeutic target for CRC.

Keywords: ASXL1, circ-ITGA7, colorectal cancer, miR-3187-3p, proliferation

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