Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer  

作　　者：SHAN JIANG XIUFENG LIN YANFEI CHEN XINNING LI JIALI KANG 

机构地区：[1]Department of Gynecology and Obstetrics,The First Affiliated Hospital of Jinan University,Guangzhou,510180,China [2]Reproductive Medical Center,Boai Hospital of Zhongshan Affiliated to Southern Medical University,Zhongshan,528400,China [3]Department of Gynecology and Obstetrics,Boai Hospital of Zhongshan Affiliated to Southern Medical University,Zhongshan,528400,China [4]Department of Gynecology and Obstetrics,Guangzhou First People’s Hospital,Guangzhou Medical University,Guangzhou,510180,China

出　　处：《BIOCELL》2024年第8期1265-1273,共9页生物细胞（英文）

摘　　要：Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and development.However,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still unclear.Methods:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian carcinoma.Cytotoxicity assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer cells.RNA pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer cells.Results:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian cancer.Functional experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this function.Mechanistically,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

关 键 词：Ultra-conserved non-coding RNA uc.243 Drug efflux Drug transporters Chemoresistance Ovarian cancer 

分 类 号：R737.31[医药卫生—肿瘤]