CircRNA circ_0005273 contributes to the cisplatin resistance of cervical cancer cells by sponging miR-133b
Creators: name: Wu, Lixia
name: Gao, Jing
name: Liu, Subin
name: Jia, Yuling
name: Li, Cairan
name: Duan, Lihong
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biophysics
subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Statistics
subject: FOS: Mathematics
subject: Hematology

description: Circular RNAs (circRNAs) have been found to play important roles in drug resistance of human neoplasms. The aim of this study was to explore the effect of circ_0005273 on cisplatin (DDP) resistance of cervical cancer (CC) cells and identify its underlying mechanism. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyse circ_0005273 and miR-133b expressions, and cell counting kit-8 (CCK-8), Hoechst 33258 staining and caspase-3 activity analysis were performed to evaluate cell proliferation and apoptosis. Luciferase reporter, RNA binding protein immunoprecipitation (RIP) and RNA pull down assays were applied to explore the interaction between circ_0005273 and miR-133b. Our research showed that circ_0005273 and miR-133b expressions were upregulated and downregulated in DDP-resistant CC cancer tissues and cell lines, respectively. Both of circ_0005273 and miR-133b levels were correlated with FIGO stage, DDP status and overall survival rates. Knockdown of circ_0005273 enhanced the sensitivity of DDP-resistant CC cells to DDP by inhibiting cell proliferation and promoting cell apoptosis. Furthermore, circ_0005273 acts as a competing endogenous RNA to modulate miR-133b expression. Downregulation of miR-133b partly reversed the DDP sensitivity of circ_0005273 knockdown in DDP-resistant CC cells. In summary, our study elucidated the role of circ_0005273/miR-133b axis in DDP resistance of CC cells, which might be a potential therapeutic target for DDP-resistant CC patients.
Impact Statement<b>What is already known on this subject?</b> The detailed regulatory mechanisms underlying DDP chemoresistance are still unclear. Recently, literatures reported that circ_0005273 exerts a regulatory role in the tumorigenesis and progression of human cancers including thyroid carcinoma, pancreatic carcinoma, colorectal carcinoma and breast carcinoma.<b>What do the results of this study add?</b> Circ_0005273 contributes to the DDP resistance of CC cells via sponging miR-133b.<b>What are the implications of these findings for clinical practice and/or further research?</b> The results help to reverse DDP chemoresistance, and the circ_0005273/miR-133b axis might be a potential therapeutic target for DDP-resistant CC patients. <b>What is already known on this subject?</b> The detailed regulatory mechanisms underlying DDP chemoresistance are still unclear. Recently, literatures reported that circ_0005273 exerts a regulatory role in the tumorigenesis and progression of human cancers including thyroid carcinoma, pancreatic carcinoma, colorectal carcinoma and breast carcinoma. <b>What do the results of this study add?</b> Circ_0005273 contributes to the DDP resistance of CC cells via sponging miR-133b. <b>What are the implications of these findings for clinical practice and/or further research?</b> The results help to reverse DDP chemoresistance, and the circ_0005273/miR-133b axis might be a potential therapeutic target for DDP-resistant CC patients.