CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis  

作　　者：JIANYUN XIE LINIE LU JIALI ZHANG QIRUI LI WEIDONG CHEN 

机构地区：[1]Depatment of Urology,The Affliated People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou,China [2]Department of Internal Medicine Outpatient ainic,The Afliated People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou,China

出　　处：《Oncology Research》2024年第3期529-544,共16页肿瘤学研究（英文）

基　　金：Fujian Provincial Health and Middleaged and Young Backbone Talents Training Project“The role and Mechanism of C53 in mcRPC Treatment of Drug Resistance”(2019-ZQN-77).

摘　　要：Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.

关 键 词：circTHSD4 Docetaxel resistance Prostate cancer miR-203 HMGA2 

分 类 号：R737.25[医药卫生—肿瘤]