title: TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFβR2/p-Smad3 signals.
abstract: Testicular nuclear receptor 4 (TR4), a member of the nuclear receptor superfamily, may play important roles to modulate the metabolic diseases and prostate tumorigenesis. Here we found TR4 could increase prostate cancer (PCa) cell invasion. Mechanism dissection revealed that TR4 might increase PCa cell invasion via decreasing the miR-373-3p expression that resulted in the activation of the TGFβR2/p-Smad3 signals. The in vivo mouse model using orthotopically xenografted CWR22Rv1 cell line transfected with luciferase-reporter confirmed in vitro cell line studies showing TR4 increased PCa metastasis via decreasing the miR-373-3p expression. Together, these data suggest that TR4 may increase PCa metastasis via a newly identified signal and targeting these TR4/miR-473-3p/TGFβR2/p-Smad3 signals using TR4 antagonist or TR4-siRNA or miR-373-3p may allow us to develop a new potential therapeutic approach to better suppress PCa metastasis.
authors.affiliation: Department of Urology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.|George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Xiaofu
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Urology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.|George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Fan
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Dong-Rong
authors.initials: DR
authors.lastname: Yang
authors.affiliation: Chawnshang Chang Liver Cancer Center, Department of Urology, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Gonghui
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Urology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China.|George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yang
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology 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: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011987:Receptors, Steroid / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: C527114:MIRN373 microRNA, human; D035683:MicroRNAs; C490515:NR2C2 protein, human; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: TR4; metastasis; miR-373-3p; prostate cancer