miR-150 Modulates Cisplatin Chemosensitivity and Invasiveness of Muscle-Invasive Bladder Cancer Cells via Targeting PDCD4 In Vitro
Ye Lei, Xiheng Hu, Bin Li, Minyuan Peng, Shiyu Tong, Xiongbing Zu, Zhi Wang, Lin Qi, Minfeng Chen
Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
Med Sci Monit 2014; 20:1850-1857
Chemotherapeutic insensitivity and tumor cell invasiveness are major obstacles to effectively treating muscle-invasive bladder cancer (MIBC). Recent reports show that microRNAs (miRNAs) play an important role in the chemotherapeutic response and disease progression of MIBC. Therefore, here we investigated the role of miR-150 in MIBC cells in vitro.
Material and Methods: miR-150 expression was quantified by qRT-PCR in two MIBC cell lines (5637 and T24). After successful miR-150 inhibition by transfection, MTS and transwell assays were used to assess the MIBC’s cisplatin sensitivity and cell invasiveness, respectively. The TargetScan database and a luciferase reporter system were used to identify whether the programmed cell death 4 protein (PDCD4) is a direct target of miR-150 in MIBC cells.
Results: miR-150 expression was found to be significantly increased in both MIBC cell lines, and treatment with a miR-150 inhibitor significantly sensitized MIBC cells to cisplatin and inhibited MIBC cell invasiveness. PDCD4 was identified as a direct target of miR-150 in MIBC cells, and increased PDCD4 expression via transfection with the pLEX-PDCD4 plasmid efficiently sensitized MIBC cells to cisplatin chemotherapy and inhibited MIBC cell invasiveness.
Conclusions: This study provides novel evidence that miR-150 functions as a tumor promoter in reducing chemosensitivity and promoting invasiveness of MIBC cells via targeting PDCD4. Thus, modulation of the miR-150-PDCD4 axis shows promise as a therapeutic strategy for MIBC.
Keywords: Antineoplastic Agents - pharmacology, Apoptosis Regulatory Proteins - metabolism, Base Sequence, Cell Line, Tumor, Cisplatin - pharmacology, DNA Primers, Disease Progression, MicroRNAs - physiology, Neoplasm Invasiveness, RNA-Binding Proteins - metabolism, Urinary Bladder Neoplasms - pathology