<p>circRNA MYLK Accelerates Cervical Cancer via Up-Regulation of RHEB and Activation of mTOR Signaling</p>

Abstract

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.

RETRACTED ARTICLE: Has_circ_0008583 modulates hepatocellular carcinoma progression through the miR-1301-3p/METTL3 pathway

“…Studies have shown that miR-1301-3p plays a dual role in tumor progression and can be used as a prognostic biomarker and therapeutic target for some malignant tumors [ 21–24 ]. In addition, miR-1301-3p was sponged by Circ_0004370, CircRNA MYLK and participated in cancer progression [ 25 , 26 ]. Here, our results showed that miR-1301-3p mimic could partially reverse the effect of hsa_circ_0008583 overexpression on HCC cell progression, which indicated that hsa_circ_0008583 played a carcinogenic role in HCC by sponging miR-1301-3p.…”

Circular RNA circ_0000228 promotes the malignancy of cervical cancer via microRNA-195-5p/ lysyl oxidase-like protein 2 axis

“…For instance, circ_0000069 enhances the growth, migration, and invasion of CC cells via miR-873-5p/TUSC3 axis [ 19 ]. circ_MYLK facilitates CC progression by up-modulating RHEB and activating the mTOR signaling pathway [ 20 ]. Circ_AKT1 accelerates CC progression by up-modulating AKT1 through miR-942-5p [ 21 ].…”

hsa_circ_0101119 facilitates the progression of cervical cancer via an interaction with EIF4A3 to inhibit TCEAL6 expression

“…For instance, circ-MYB proto-oncogene like 2 is reported to facilitate the proliferation and invasion of cc cells (37). Moreover, chen et al (38) suggested that circrna myosin light chain kinase could accelerate cell proliferation with si-hsa_circ_0101119 and sh-TCEAL6, HeLa cell proliferation was determined using an EdU assay (magnification, x200). (C) After co-transfection with si-hsa_circ_0101119 and sh-TCEAL6, the colony numbers of HeLa cells were detected with a colony formation assay (magnification, x100).…”

“…For instance, circ-MYB proto-oncogene like 2 is reported to facilitate the proliferation and invasion of CC cells ( 37 ). Moreover, Chen et al ( 38 ) suggested that circRNA myosin light chain kinase could accelerate cell proliferation and repress apoptosis via the upregulation of Ras homolog, mTORC1 binding and the activation of the mTOR pathway in CC. Wang et al ( 39 ) also revealed that the overexpression of hsa_circ_0001038 could promote cell proliferation and invasion by regulating cyclin-M3 and metastasis-associated in colon cancer 1 expression in CC.…”