Cancer Management and Research (May 2020)
circRNA MYLK Accelerates Cervical Cancer via Up-Regulation of RHEB and Activation of mTOR Signaling
Abstract
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 ChinaCorrespondence: Jingxin ChengDepartment of Gynecology, East Hospital Affiliated to Tongji University, No.1800 Yuntai Road, Pudong New Area, Shanghai 200012, People’s Republic of ChinaEmail [email protected]: 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
