title: Androgen receptor regulates SRC expression through microRNA-203.
abstract: The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures. Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3' UTR of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens. We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203.
authors.affiliation: Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.|Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Man Kit
authors.initials: MK
authors.lastname: Siu
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.|Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Institute of Information System and Applications, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Hsiu-Lien
authors.initials: HL
authors.lastname: Yeh
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Yin
authors.affiliation: Department of Andrology, Pingtan Hospital of Traditional Chinese Medicine, Fujian, China.
authors.forename: Shih-Yang
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.|Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Nien
authors.initials: YN
authors.lastname: Liu
mesh_terms: D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C410798:AR protein, human; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen; D019061:src-Family Kinases
keywords: SRC; androgen receptor (AR); microRNA (miR)-203; prostate cancer (PCa)