title: Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals.
abstract: Increasing evidence has demonstrated that the androgen receptor (AR) plays important roles to promote the metastasis of clear cell renal cell carcinoma (ccRCC). The detailed mechanisms, especially how AR functions via altering the circular RNAs (circRNAs) remain unclear. Here we identified a new circRNA (named as circHIAT1) whose expression was lower in ccRCCs than adjacent normal tissues. Targeting AR could suppress ccRCC cell progression via increasing circHIAT1 expression. ChIP assay and luciferase assay demonstrated that AR suppressed circHIAT1 expression via regulating its host gene, Hippocampus Abundant Transcript 1 (HIAT1) expression at the transcriptional level. The consequences of AR-suppressed circHIAT1 resulted in deregulating miR-195-5p/29a-3p/29c-3p expressions, which increased CDC42 expression to enhance ccRCC cell migration and invasion. Increasing this newly identified signal via circHIAT1 suppressed AR-enhanced ccRCC cell migration and invasion. Together, these results suggested that circHIAT1 functioned as a metastatic inhibitor to suppress AR-enhanced ccRCC cell migration and invasion. Targeting this newly identified AR-circHIAT1-mediated miR-195-5p/29a-3p/29c-3p/CDC42 signals may help us develop potential new therapies to better suppress ccRCC metastasis.
authors.affiliation: Department of Urology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Wang
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Department of Urology, Shengjing Hospital, China Medical University, Shenyang, 110004, China. Electronic address: feixiangurology@126.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fei
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14642, USA; Sex Hormone Research Center, China Medical University/Hospital, Taichung, 404, Taiwan. Electronic address: chang@urmc.rochester.edu.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D000079962:RNA, Circular; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C410798:AR protein, human; C108259:HiAT1 transporter; C552722:MIRN195 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D009004:Monosaccharide Transport Proteins; D000079962:RNA, Circular; D011944:Receptors, Androgen; D012313:RNA; D020764:cdc42 GTP-Binding Protein
keywords: Androgen receptor; CDC42; Invasion; Migration; Renal cell carcinoma; circRNA