title: Hsa-miR-146a-5p modulates androgen-independent prostate cancer cells apoptosis by targeting ROCK1.
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.
  
  
  CONCLUSIONS
  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: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors: Bin
authors: B
authors: Xu
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors: Yeqing
authors: Y
authors: Huang
authors: Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, China.
authors: Xiaobing
authors: X
authors: Niu
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors: Tao
authors: T
authors: Tao
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors: Liang
authors: L
authors: Jiang
authors: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Na
authors: N
authors: Tong
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors: Shuqiu
authors: S
authors: Chen
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors: Ning
authors: N
authors: Liu
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors: Weidong
authors: W
authors: Zhu
authors: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors: Ming
authors: M
authors: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060787:Neoplasm Grading; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D053148:Caspase 3
keywords: ROCK1; apoptosis; miR-146a; prostate cancer