Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer
SHAN JIANG1,2, XIUFENG LIN2, YANFEI CHEN3, XINNING LI3, JIALI KANG1,4,*
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
* Corresponding Author: JIALI KANG. Email: 
(This article belongs to the Special Issue: Subcellular Organelles and Cellular Molecules: Localization, Detection, Prediction, and Diseases)
BIOCELL https://doi.org/10.32604/biocell.2024.051478
Received 06 March 2024; Accepted 29 April 2024; Published online 07 June 2024
Abstract
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.
Keywords
Ultra-conserved non-coding RNA; uc.243; Drug efflux; Drug transporters; Chemoresistance; Ovarian cancer
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