Circular RNA circ_0023404 serves as a miR‐636 sponge to promote malignant behaviors in cervical cancer cells through upregulation of CYP2S1

Abstract

Cervical cancer is the most common malignant gynecological tumor. Circular RNA (circRNA) circ_0023404 is reported to be upregulated in cervical cancer cells. This aim is to explore the role and mechanism of circ_0023404 in cervical cancer. circ_0023404, microRNA‐636 (miR‐636), and cytochrome P450 2S1 (CYP2S1) levels were detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell proliferation, migration, invasion, and apoptosis were detected by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay, 5‐ethynyl‐2′‐deoxyuridine (EDU) assay, colony formation assay, transwell assay, and cytometry assay. Protein levels of cyclin D1, matrix metallopeptidase 9 (MMP9), Bcl‐2‐associated X protein (Bax), and CYP2S1 were examined by western blot assay. The binding relationship between miR‐636 and circ_0023404 or CYP2S1 was predicted by Circinteractome or targetscan, and then verified by a dual‐luciferase reporter assay and RNA pull‐down assay. circ_0023404 and CYP2S1 expression were increased, and miR‐636 was decreased in cervical cancer tissues and cells. Moreover, circ_0023404 knockdown could repress proliferation, migration, invasion, and promote apoptosis of cervical cancer cells in vitro. Mechanically, circ_0023404 could regulate CYP2S1 expression by sponging miR‐636. circ_0023404 silencing could attenuate the progression of cervical cancer cells partly by targeting the miR‐636/CYP2S1 axis, hinting at a promising therapeutic target for cervical cancer.

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential

“…In further assessment of the effect of this circRNA on malignant characteristics of CC, in vitro hsa_circ_0023404 sponged miR-636 which allowed for increased expression of protein coding gene target CYP2S1. This hsa_circ_0023494/miR-636/CYPS21 axis resulted in downstream malignant phenotypes including increased proliferation, migration, invasion, and decrease in apoptosis [135]. Together, these data suggest hsa_circ_0023404 as a potential target in CC therapy.…”

Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer

“…Another example is bta-miR-26a which also reduced the abundance of PCK1 [44,45]. Moreover, the oncosuppressor miR-20a-3p was identified in melanoma, tongue squamous cell carcinoma, and hepatocellular carcinoma, and the oncosuppressor miR-636 was also identified in lung cancer, nasopharyngeal carcinoma, cervical cancer, endometrial cancer, ovarian cancer, and hepatocellular carcinoma [46][47][48][49][50][51][52][53][54][55][56]. It was reported that high miR-20a-3p and miR-636 expression were correlated with poor OS of CRC patients and this was consistent with our results.…”