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

circRNA MYLK 通过上调 RHEB 和激活 mTOR 信号加速宫颈癌

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作者:Rui Chen, Luning Mao, Rui Shi, Wenjing Wang, Jingxin Cheng

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.

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.

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.

Purpose

Our study focused on the function of circRNA MYLK (myosin light chain kinase), one novel tumor-related circRNA, in CC cell behaviors.

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.

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