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	Xiaofu Qiu, Jin Zhu, Yin Sun, Kun Fan, Dong-Rong Yang, Gonghui Li, Guosheng Yang, Chawnshang Chang
Journal	Oncotarget (Oncotarget) Vol. 6 Issue 17 Pg. 15397-409 (Jun 20 2015) ISSN: 1949-2553 [Electronic] United States
PMID	25980442 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	MIRN373 microRNA, human MicroRNAs NR2C2 protein, human RNA, Small Interfering Receptors, Steroid Receptors, Thyroid Hormone Receptors, Transforming Growth Factor beta SMAD3 protein, human Smad3 Protein Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II
Topics	Animals Cell Line, Tumor Cell Movement Cell Proliferation (genetics) Cell Transformation, Neoplastic (genetics) Gene Expression Regulation, Neoplastic Humans Male Mice Mice, Nude MicroRNAs (biosynthesis, genetics) Neoplasm Invasiveness (pathology) Neoplasm Transplantation Prostatic Neoplasms (pathology) Protein Serine-Threonine Kinases (metabolism) RNA Interference RNA, Small Interfering Receptor, Transforming Growth Factor-beta Type II Receptors, Steroid (metabolism) Receptors, Thyroid Hormone (metabolism) Receptors, Transforming Growth Factor beta (metabolism) Signal Transduction (genetics) Smad3 Protein (metabolism) Transplantation, Heterologous

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