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circRNA MYLK Accelerates Cervical Cancer via Up-Regulation of RHEB and Activation of mTOR Signaling

Authors Chen R, Mao L, Shi R, Wang W, Cheng J

Received 11 November 2019

Accepted for publication 18 March 2020

Published 19 May 2020 Volume 2020:12 Pages 3611—3621

DOI https://doi.org/10.2147/CMAR.S238172

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Rui Chen,1 Luning Mao,2 Rui Shi,1 Wenjing Wang,1 Jingxin Cheng1

1Department of Gynecology, East Hospital Affiliated to Tongji University, Shanghai 200012, People’s Republic of China; 2Department of Pathology, Basic Medical College, Fudan University, Shanghai 200032, People’s Republic of China

Correspondence: Jingxin Cheng
Department of Gynecology, East Hospital Affiliated to Tongji University, No.1800 Yuntai Road, Pudong New Area, Shanghai 200012, People’s Republic of China
Email jing74070336033@163.com

Background: Growing evidence directly suggested that circular RNAs (circRNAs) are crucial contributors in the course of cervical cancer (CC) onset and progression. Nevertheless, a large number of circRNAs have not been fully addressed in their function and underlying mechanisms during CC etiology.
Purpose: Our study focused on the function of circRNA MYLK (myosin light chain kinase), one novel tumor-related circRNA, in CC cell behaviors.
Methods: Firstly, we evaluated the expression profile of circMYLK in CC cells and in normal Ect1/E6E7 cell line. Moreover, the accurate function of circMYLK in CC cells was assessed via colony formation, CCK-8, EdU, and TUNEL assay. The association among circRNAs, miRNA, and target mRNAs was predicated by bioinformatics methods and validated in mechanical assays.
Results: We disclosed that circMYLK was up-regulated in CC cell lines and acted as a sponge of miR-1301-3p. Besides, downstream miR-1301-3p was capable of reversing circMYLK-mediated CC cell growth and apoptosis. Furthermore, we validated that circMYLK bound to miR-1301-3p as a sponge to upregulate RHEB (Ras homolog, mTORC1 binding) expression. As annotated in prior works, RHEB was responsible for mTOR signaling transduction. Therefore, we investigated whether circMYLK functioned its tumor-facilitating impact in CC through a RHEB-dependent mTOR signaling activation.
Conclusion: It was unveiled that circMYLK sponged miR-1301-3p to promote RHEB expression, which resulted in mTOR signaling activation and CC cell malignant growth.

Keywords: circMYLK, miR-1301-3p, RHEB, mTOR signaling, cervical cancer

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