Bin Xu1,2, Yeqing Huang1,2, Xiaobing Niu3, Tao Tao1,2, Liang Jiang1,2, Na Tong4,5, Shuqiu Chen1, Ning Liu1, Weidong Zhu1, Ming Chen1,2. 1. Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China. 2. Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. 3. Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, China. 4. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China. 5. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Abstract
BACKGROUND: MicroRNAs (miRNAs) have been demonstrated playing important roles in the procession of prostate cancer cells transformation from androgen-dependence to androgen-independence. METHODS: We conducted the miRNA microarray and realtime PCR analyses in both androgen-dependent (ADPC) and androgen-independent prostate cancer (AIPC) tissues. We also explored the role of hsa-miR-146a-5p (miR-146a) in MSKCC prostate cancer clinical database. Moreover, the impact of miR-146a on prostate cancer cells apoptosis were detected by Hoechst staining and fluorescence-activated cell sorter (FACS). Its target is predicted by DIANA LAB online database and the result was assumed by western blotting and luciferase assay. RESULTS: We demonstrated that miR-146a was down-regulated in AIPC tissues and cell lines compared to that in the ADPC tissues. In MSKCC data re-analyses, we found that miR-146a was underexpressed in metastatic prostate cancer tissues and those with Gleason score >8, moreover, low level of miR-146a represented a high biochemical relapse rate after radical prostatectomy. In the functional analyses, we transfected miR-146a mimics into CPRC cell lines and found miR-146a induced cells apoptosis. In mechanic analyses, we found that miR-146a inhibited the basal level of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) expression by targeting its 3'UTR and an inverse correlation of expression between miR-146a and ROCK1 was observed. Moreover, caspase 3 activity was stimulated by miR-146a overexpression. CONCLUSION: miR-146a has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic strategy for future personalized anti-cancer treatment.
BACKGROUND: MicroRNAs (miRNAs) have been demonstrated playing important roles in the procession of prostate cancer cells transformation from androgen-dependence to androgen-independence. METHODS: We conducted the miRNA microarray and realtime PCR analyses in both androgen-dependent (ADPC) and androgen-independent prostate cancer (AIPC) tissues. We also explored the role of hsa-miR-146a-5p (miR-146a) in MSKCC prostate cancer clinical database. Moreover, the impact of miR-146a on prostate cancer cells apoptosis were detected by Hoechst staining and fluorescence-activated cell sorter (FACS). Its target is predicted by DIANA LAB online database and the result was assumed by western blotting and luciferase assay. RESULTS: We demonstrated that miR-146a was down-regulated in AIPC tissues and cell lines compared to that in the ADPC tissues. In MSKCC data re-analyses, we found that miR-146a was underexpressed in metastatic prostate cancer tissues and those with Gleason score >8, moreover, low level of miR-146a represented a high biochemical relapse rate after radical prostatectomy. In the functional analyses, we transfected miR-146a mimics into CPRC cell lines and found miR-146a induced cells apoptosis. In mechanic analyses, we found that miR-146a inhibited the basal level of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) expression by targeting its 3'UTR and an inverse correlation of expression between miR-146a and ROCK1 was observed. Moreover, caspase 3 activity was stimulated by miR-146a overexpression. CONCLUSION:miR-146a has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic strategy for future personalized anti-cancer treatment.
Authors: Yeqing Huang; Tao Tao; Chunhui Liu; Han Guan; Guangyuan Zhang; Zhixin Ling; Lei Zhang; Kai Lu; Shuqiu Chen; Bin Xu; Ming Chen Journal: Int J Oncol Date: 2017-01-05 Impact factor: 5.650