rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS

作者全名："Qiao, Deqian; Liu, Yiling; Lei, Yunlong; Zhang, Chundong; Bu, Youquan; Tang, Yishu; Zhang, Ying"

作者地址："[Qiao, Deqian; Liu, Yiling; Lei, Yunlong; Zhang, Chundong; Bu, Youquan; Zhang, Ying] Chongqing Med Univ, Sch Basic Med, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Qiao, Deqian; Liu, Yiling; Lei, Yunlong; Zhang, Chundong; Bu, Youquan; Zhang, Ying] Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China; [Tang, Yishu] Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Zhang, Y (通讯作者)，Chongqing Med Univ, Sch Basic Med, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China.; Zhang, Y (通讯作者)，Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China.; Tang, YS (通讯作者)，Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：FRONTIERS IN BIOSCIENCE-LANDMARK

ESI学科分类：　

WOS号：WOS:001010678100010

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：28

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：prostate cancer; chemoresistance; sncRNA; rsRNA; PTGIS

摘要："Background: rRNA-derived small RNAs (rsRNAs) represent a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of rRNAs; however, their roles in tumor development are unclear. In the present study, we explored the effect of a kind of rsRNA-28S, which originates from 28S rRNA, on the chemoresistance of prostate cancer cells and the mechanisms underlying its effect. Methods: Quantitative reverse transcription PCR (RT-PCR) was performed to quantify rsRNA-28S levels in serum samples taken from prostate cancer patients. DU-145R cells, which are resistant to both paclitaxel and docetaxel, were generated from parental DU-145 cells. Northern blot was conducted to detect cellular rsRNA-28S levels following drug treatments. To verify the effect of rsRNAs-28S on chemoresistance, antisense oligonucleotides were utilized to block rsRNA-28S functions, and a series of assays were further performed, such as cell viability, cell proliferation, colony formation and tumor sphere formation. The target gene of rsRNA-28S was explored using dual-luciferase reporter gene assay. Results: The rsRNA-28S level was reduced in the serum samples of patients who received chemotherapy compared to that of patients who did not. Furthermore, the rsRNA-28S level was remarkably declined in DU-145R cells, and drug treatments decreased the levels of rsRNA-28S in DU-145 and DU-145R cells. Moreover, rsRNA-28S inhibition enhanced the chemoresistance of prostate cancer cells as well as their cancer stem cell characteristics. Mechanistically, the prostaglandin I2 synthase (PTGIS) gene transcript was verified as a target of rsRNA-28S, as rsRNA-28S inhibited the translation of PTGIS mRNA by directly binding the 3 ' untranslated region of PTGIS mRNA. rsRNA-28S inhibition was also found to increase PTGIS abundance, and PTGIS overexpression significantly enhanced prostate cancer cell chemoresistance. Conclusions: Our findings indicate that rsRNA-28S attenuates prostate cancer cell chemoresistance by downregulating its target gene PTGIS. This study not only greatly contributes to systematic identification and functional elucidation of chemoresistance relevant rsRNAs, but also promotes rsRNA-included combinatorial therapeutic regimens for cancer."

基金机构："National Natural Science Foundation of China [82173243, 81872014, 81672301]; Scientific and Technological Research Projects of Chongqing Education Commission [KJQN202100403]; Chongqing Natural Science Foundation [CSTB2022NSCQ-MSX0123]"

基金资助正文："Funding This study was supported by the National Natural Science Foundation of China (82173243, 81872014, 81672301) , Scientific and Technological Research Projects of Chongqing Education Commission (KJQN202100403) and Chongqing Natural Science Foundation (CSTB2022NSCQ-MSX0123) ."