miR-34b-3p 通过调控 CCND2 和 P2RY1 基因抑制膀胱癌多药耐药。

MiR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.

机构信息

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).

出版信息

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.

背景

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。

材料与方法

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。