RBM15‑mediating MDR1 mRNA m<sup>6</sup>A methylation regulated by the TGF‑β signaling pathway in paclitaxel‑resistant ovarian cancer

Yuan,Jia; Yuan,Jia; Guan,Wencai; Guan,Wencai; Li,Xin; Li,Xin; Wang,Fanchen; Wang,Fanchen; Liu,Huiqiang; Liu,Huiqiang; Xu,Guoxiong; Xu,Guoxiong

doi:10.3892/ijo.2023.5560

RBM15‑mediating MDR1 mRNA m⁶A methylation regulated by the TGF‑β signaling pathway in paclitaxel‑resistant ovarian cancer

Authors:
- Jia Yuan
- Wencai Guan
- Xin Li
- Fanchen Wang
- Huiqiang Liu
- Guoxiong Xu
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Affiliations: Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
Published online on: August 11, 2023 https://doi.org/10.3892/ijo.2023.5560
Article Number: 112
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer (OC) lacks effective biomarkers for diagnosis at an early stage and often develops chemoresistance after the initial treatment at an advanced stage. RNA‑binding motif protein 15 (RBM15) is an RNA m6A methylation mediator that serves an oncogenic role in some cancers. However, the function and molecular mechanisms of RBM15 in ovarian tumorigenesis and chemoresistance remain to be elucidated. The present study identified the overexpression of RBM15 in OC tissues and paclitaxel (PTX)‑resistant cells using reverse transcription‑quantitative (q)PCR, western blotting and immunohistochemistry. Clinical data analyses showed that high expression of RBM15 was associated with poor prognosis in patients with OC. Overexpression of RBM15 led to an increase in cell viability and colony formation and a decrease in cell sensitivity to PTX and apoptosis, whereas the knockdown of RBM15 resulted in the inhibition of cell viability and colony formation in vitro and tumor formation in vivo and increased cell apoptosis and sensitivity to PTX in a time‑ and dose‑dependent manner. Furthermore, RBM15 knockdown reduced the spheroid formation of PTX‑resistant OC cells. Silencing of RBM15 decreased multidrug resistance 1 (MDR1) mRNA m⁶A methylation detected by the methylated RNA immunoprecipitation‑qPCR assay and downregulated the expression of a chemo‑drug efflux pump MDR1 at the mRNA and protein levels. Finally, RBM15 expression was suppressed by the activation of the TGF‑β signaling pathway. Thus, the findings revealed a TGF‑β/RBM15/MDR1 regulatory mechanism. Targeting RBM15 may provide a novel therapeutic strategy for the treatment of PTX‑resistant OC.

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