Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Institute of Urology, Anhui Medical University, Hefei, Anhui, China (mainland).
Med Sci Monit. 2019 Feb 19;25:1323-1335. doi: 10.12659/MSM.913746.
BACKGROUND Chemoresistance is a main limitation in chemotherapy for therapeutic cancer. MicroRNA (miRNA) has been indicated in the progression and tumorigenesis of many types of cancer, but the effect of miR-34b-3p in bladder cancer (BCa) cells is still unknown. MATERIAL AND METHODS This research compared the multidrug-sensitive (5637) BCa cell line and the multidrug-resistant (EJ) BCa cell line. We found that CCND2 (G1/S-specific cyclin-D2) and P2RY1 (purinergic receptor P2Y1) were the targets of miR-34b-3p, as further validated by qRT-PCR (quantitative real-time polymerase chain reaction) and western blot analysis. RESULTS Forced reversal of the levels of miR-34b-3p or CCND2/P2RY1 changed the chemoresistance profiles in both 5637 cells and EJ cells. Further experiments suggested that the CCND2 gene and the P2RY1 gene act in concert to negatively correlate with miR-34b-3p effect on BCa multidrug-chemoresistance. CONCLUSIONS These results not only reveal new players regulating BCa chemoresistance, but also provide clues for effective chemotherapy for BCa patients.
化疗耐药性是癌症治疗中化疗的主要限制因素。微小 RNA(miRNA)已被证实参与多种类型癌症的进展和肿瘤发生,但 miR-34b-3p 在膀胱癌(BCa)细胞中的作用尚不清楚。
本研究比较了多药敏感(5637)BCa 细胞系和多药耐药(EJ)BCa 细胞系。我们发现 CCND2(G1/S 特异性细胞周期蛋白 D2)和 P2RY1(嘌呤能受体 P2Y1)是 miR-34b-3p 的靶标,这进一步通过 qRT-PCR(实时定量聚合酶链反应)和 Western blot 分析得到验证。
强制逆转 miR-34b-3p 或 CCND2/P2RY1 的水平改变了 5637 细胞和 EJ 细胞的化疗耐药谱。进一步的实验表明,CCND2 基因和 P2RY1 基因协同作用,与 miR-34b-3p 对 BCa 多药化疗耐药性的影响呈负相关。
这些结果不仅揭示了调节 BCa 化疗耐药性的新靶点,也为 BCa 患者的有效化疗提供了线索。