circRNA MYLK Accelerates Cervical Cancer via Up-Regulation of RHEB and Activation of mTOR Signaling
| Autor: | Jingxin Cheng, Rui Chen, Luning Mao, Wenjing Wang, Rui Shi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Myosin light-chain kinase biology Cell growth Cell MYLK mTORC1 Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology Downregulation and upregulation 030220 oncology & carcinogenesis microRNA biology.protein medicine RHEB |
| Zdroj: | Cancer Management and Research. 12:3611-3621 |
| ISSN: | 1179-1322 |
| DOI: | 10.2147/cmar.s238172 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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