title: Regulation of Docetaxel Sensitivity in Prostate Cancer Cells by hsa-miR-125a-3p via Modulation of Metastasis-Associated Protein 1 Signaling.
abstract: OBJECTIVE
  To identify the potential downstream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa).
  
  
  METHODS
  The expression levels of hsa-miR-125a-3p were assessed in chemoresistant PCa tissues and experimentally established chemoresistant cells using quantitative reverse transcription-polymerase chain reaction. The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R). Finally, using multiple assays, the regulation of metastasis-associated protein 1 (MTA1), an essential component of the Mi-2-nucleosome remodeling deacetylation complex, by hsa-miR-125a-3p was studied at both molecular and functional levels.
  
  
  RESULTS
  The expression of hsa-miR-125a-3p was significantly downregulated in chemoresistant PCa tissues and cells. Inhibition of hsa-miR-125a-3p significantly increased docetaxel (Dox) resistance in PC-3 cells, whereas upregulation of hsa-miR-125a-3p effectively reduced Dox resistance in PC-3R, suggesting that this microRNA (miRNA) may act as a tumor suppressor along the pathogenesis of drug resistance. Mechanistically, hsa-miR-125a-3p induced apoptosis and Dox sensitivity in PCa cells through regulating MTA1.
  
  
  CONCLUSIONS
  Our results collectively indicate that miRNA-MTA1 can form a delicate regulatory loop to maintain a bistable state in the Dox chemosensitivity, and future endeavor in this filed should provide important clues to develop miRNA-based therapies that benefit advanced PCa patients through modulating the functional status of MTA1.
authors.affiliation: Department of Urology, Baoji Central Hospital, Baoji, Shaanxi Province, China.
authors.forename: Jian-Zhou
authors.initials: JZ
authors.lastname: Liu
authors.affiliation: Department of Urology, Baoji Central Hospital, Baoji, Shaanxi Province, China.
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Yin
authors.affiliation: Xi'an Health Management Service Center, Xi'an, Shaanxi Province, China.
authors.forename: Chang-You
authors.initials: CY
authors.lastname: Yan
authors.affiliation: Department of Medical Psychology, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Baoji Central Hospital, Baoji, Shaanxi Province, China. Electronic address: luoxiaohuidoctor@163.com.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Luo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D000077143:Docetaxel / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators
chemical_list: D000970:Antineoplastic Agents; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D000077143:Docetaxel; D006655:Histone Deacetylases