CircFAT1 facilitates cervical cancer malignant progression by regulating ERK1/2 and p38 MAPK pathway through miR‐409‐3p/CDK8 axis

• DOI: 10.1002/ddr.21816
• Publication Date: 2021-04-05T12:50:09Z
• Authors: Bing Zhou; Ting Li; Rongping Xie; Jianbin Zhou; Jue Liu; Yu Luo; Xia Zhang
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; MAP Kinase Signaling System; Uterine Cervical Neoplasms; RNA, Circular; Cadherins; Cyclin-Dependent Kinase 8; p38 Mitogen-Activated Protein Kinases; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Disease Progression; Animals; Humans; Female; Extracellular Signal-Regulated MAP Kinases

Abstract Circular RNA FAT atypical cadherin 1 (circFAT1) has been reported to play vital roles in the progression of some cancers. However, regulatory role and underlying mechanisms circFAT1 cervical cancer (CC) remain largely unknown. The expression circFAT1, microRNA (miR)‐409‐3p cyclin‐dependent kinase 8 (CDK8) was detected using qRT‐PCR Western blot assays. Cell proliferation, apoptosis, migration invasion vitro were investigated cell counting kit‐8, colony formation, flow cytometry, transwell assays, respectively. assay used determine activation ERK1/2 p38 MAPK pathway. interaction miR‐409‐3p or CDK8 confirmed by dual‐luciferase reporter, pull‐down RIP effects vivo determined xenograft models. CircFAT1 highly expressed CC, closely associated with poor prognosis. knockdown resulted suppression invasion, promotion apoptosis CC cells via inactivation pathway; also, silencing could inactivate this pathway repressed tumor growth vivo. Mechanistic analysis showed that directly sponged then relieved repressive effect on its target CDK8. Furthermore, inhibition reversed cells. Whereas, overexpression impeded motility, which attenuated promoted activating through miR‐409‐3p/CDK8 axis, suggesting a promising prognostic biomarker therapeutic for CC.