IMR Press / FBL / Volume 28 / Issue 5 / DOI: 10.31083/j.fbl2805102
Open Access Original Research
rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS
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1 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Chongqing Medical University, 400016 Chongqing, China
2 Molecular Medicine and Cancer Research Center, Chongqing Medical University, 400016 Chongqing, China
3 Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
*Correspondence: (Yishu Tang); (Ying Zhang)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(5), 102;
Submitted: 24 February 2023 | Revised: 7 April 2023 | Accepted: 10 April 2023 | Published: 25 May 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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.

prostate cancer
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82173243/National Natural Science Foundation of China
81872014/National Natural Science Foundation of China
81672301/National Natural Science Foundation of China
KJQN202100403/Scientific and Technological Research Projects of Chongqing Education Commission
CSTB2022NSCQ-MSX0123/Chongqing Natural Science Foundation
Fig. 1.
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