TY  - EJOU
AU  - JIANG, SHAN 
AU  - LIN, XIUFENG 
AU  - CHEN, YANFEI 
AU  - LI, XINNING 
AU  - KANG, JIALI 

TI  - Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer
T2  - BIOCELL

PY  - 2024
VL  - 48
IS  - 8
SN  - 1667-5746

AB  - <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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). <b>Conclusion:</b> 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.
KW  - Ultra-conserved non-coding RNA; uc.243; Drug efflux; Drug transporters; Chemoresistance; Ovarian cancer

DO  - 10.32604/biocell.2024.051478