ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2022; 13(15):3652-3659. doi:10.7150/jca.78246 This issue Cite
Research Paper
miR-143 mediates abiraterone acetate resistance by regulating the JNK/Bcl-2 signaling pathway in prostate cancer
Surgical Department I (Urology Department), LONGHUA Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping Road South, Xuhui District, Shanghai 200032, China
#These authors contributed equally to this work
Abstract
Background: miR-143 is known to be downregulated in various cancer cells and tumors and generally plays a tumor-suppressor role. miR-143. However, the role of miR-143 in the mediation of the sensitivity of prostate cancer cells to abiraterone acetate remains unrevealed.
Methods: The expression levels of miRNAs were determined by miRNA microarray and quantitative real-time PCR (qRT-PCR). The protein levels were assessed by Western blot assay. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry.
Results: We identified that miR-143 was significantly downregulated in PC3-AbiR cells compared to PC3 cells. Overexpression of miR-143 promoted PC-AbiR sensitivity to abiraterone acetate in vitro and in vivo. We also revealed that miR-143 upregulation inhibited p-JNK (c-Jun N-terminal kinases) and increased p-Bcl2 (B-cell lymphoma 2), contributing to abiraterone acetate-induced apoptosis in PC3-AbiR cells. Finally, we showed that the combination of miR-143 and abiraterone acetate exerted the most profound tumor inhibition effect and prolonged the mice survival rate in PC3-AbiR tumor-bearing mice.
Conclusion: Upregulation of miR-143 may serve as a new strategy to enhance the therapeutical effect of abiraterone acetate on prostate cancer patients who are resistant to abiraterone acetate.
Keywords: miR-143, prostate cancer, abiraterone acetate, JNK/Bcl-2 signaling, drug resistance
Citation styles
