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Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression

Authors Zhao JP, Chen LL

Received 25 February 2020

Accepted for publication 19 June 2020

Published 10 August 2020 Volume 2020:12 Pages 7107—7116

DOI https://doi.org/10.2147/CMAR.S251180

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava


Jian Pei Zhao,1 Li Li Chen2

1Department of Anus & Intestine Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, People’s Republic of China; 2Department of Hematology and Oncology, The First People’s Hospital of Taizhou, Taizhou 318020, Zhejiang, People’s Republic of China

Correspondence: Li Li Chen
Department of Hematology and Oncology, The First People’s Hospital of Taizhou, No. 218, Hengjie Road, Huangyan District, Taizhou, Zhejiang Province, People’s Republic of China
Tel +86 15105868468
Email wangyuz1234567@sina.com

Purpose: Recently, studies have demonstrated that a novel circular RNA (circRNA), circMAT2B, can promote cell proliferation and can thus contribute to the growth and development of hepatocellular carcinoma. However, the precise mechanisms underlying in circMAT2B-induced colorectal cancer (CRC) cell proliferation are not yet fully understood.
Materials and Methods: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circMAT2B expression in 70 CRC tissues and 70 matched adjacent normal tissues, CRC cell lines and human colonic epithelial cell line (NCM460). The direct interaction between miR-610 and circMAT2B or E2F1 was verified using luciferase reporter assay and biotinylated RNA Pull-down assay. Cell Counting Kit-8, colony formation assay, flow cytometry were utilized to examine the effect of circMAT2B, miR-610 and E2F1 on cell proliferation. Western blot was conducted to evaluate E2F1 expression.
Results: In our study, circMAT2B was found to be upregulated in CRC tissues and cell lines. Furthermore, the silencing of circMAT2B significantly inhibited proliferation. Hence, in order to investigate the mechanism underlying the oncogenic properties of circMAT2B in CRC, a bioinformatics analysis (circular RNA Interactome, https://circinteractome.nia.nih.gov/) was performed to screen the putative interacting microRNAs of circMAT2B. miR-610 was identified to be one of the potential targeted miRNAs of circMAT2B. Luciferase reporter and RNA pulldown assay confirmed a direct interaction between circMAT2B and miR-610. Moreover, circMAT2B expression was negatively correlated with the expression of miR-610 in CRC tissues (r=− 0.5131, p< 0.0001). Furthermore, we demonstrated circMAT2B upregulated expression levels of the miR-610 target gene E2F1, which is involved in cell proliferation, is overexpression in a broad range of human cancer including CRC. Further studies suggested that E2F1 upregulation could significantly reverse the si-circMAT2B-mediated inhibition of proliferation.
Conclusion: circMAT2B is upregulated in CRC tissues and cell lines. Moreover, circMAT2B promoted CRC proliferation by regulating the miR-610/E2F1 axis, which may serve as a potential therapeutic target for CRC treatment.

Keywords: circMAT2B, miR-610, E2F1, colorectal cancer, proliferation

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