title: Androgen receptor promotes melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signals.
abstract: Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared with AR-negative melanoma patients. Here we report that AR can have positive roles to increase melanoma cell invasion in multiple cell lines in vitro and a mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13 signaling to increase MITF protein degradation through a reduction of de-ubiquitination. Restoring MITF can reverse AR-enhanced melanoma cell invasion. Together, our results demonstrate that AR can promote melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly identified signal with AR degradation enhancer ASC-J9 may help us to better suppress the melanoma metastasis.
authors.affiliation: Departments of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester NY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Departments of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Ou
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester NY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yeh
authors.affiliation: Departments of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Departments of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: J
authors.initials: J
authors.lastname: Long
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester NY, USA.|Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan.
authors.forename: C
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016000:Cluster Analysis; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden; D064570:Ubiquitin-Specific Proteases; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: C552081:MIRN539 microRNA, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins; D011944:Receptors, Androgen; D020794:Receptor Protein-Tyrosine Kinases; D010450:Endopeptidases; C561638:USP13 protein, human; D064570:Ubiquitin-Specific Proteases; D000094963:Axl Receptor Tyrosine Kinase