title: MicroRNA-132/212 Upregulation Inhibits TGF-β-Mediated Epithelial-Mesenchymal Transition of Prostate Cancer Cells by Targeting SOX4.
abstract: MicroRNAs (miRNAs) are noncoding RNAs that are important for embryonic stem cell development and epithelial to mesenchymal transition (EMT). Accumulating evidence indicates that miRNAs play critical roles in prostate cancer (PCa) metastasis and have potential use as therapeutic targets. Although dysregulated miR-132/212 have been suggested to be directly involved in the proliferation and invasion of multiple malignancies, the exact role of miR-132/212 in PCa has not yet been fully understood.
  
  
  
  Real-time quantitative PCR (RT-qPCR) and bioinformatics analysis were used to validate the expression levels of miR-132/212 in PCa cell lines as well as in prostatic tissues. The biological function of miR-132/212 was evaluated by MTS, transwell, and wound healing assays, respectively. RT-qPCR and Western blot were used to study the transcript and protein expression levels. Bioinformatics tools and luciferase reporter assay were utilized to identify the molecular target of miR-132/212. Immunohistochemistry (IHC) was used to detect the expression of SOX4.
  
  
  
  miR-132 and miR-212 from the same gene cluster are downregulated in human PCa tissues when compared with benign prostatic hyperplasia tissues (both P < 0.05). Functionally, upregulation of miR-132/212 inhibits the migration and invasive capacity of Vcap and Lncap cells by wound-healing and transwell assays, respectively. Notably, overexpression of miR-132/212 could inhibit TGF-β (transforming growth factor-β)-induced EMT in Vcap and Lncap cells at both the mRNA and protein expression levels. SOX4 gene, an important EMT regulator of PCa, was identified as the target of miR-132/212 by bioinformatics tools and luciferase reporter assay. Clinically, miR-132/212 expression levels were adversely correlated with Gleason score (P < 0.001) and SOX4 expression by IHC and RT-qPCR in PCa tissues.
  
  
  
  Our data suggested that miR-132/212 may act as tumor suppressors in PCa progression through disrupting EMT process by directly targeting SOX4. Prostate 76:1560-1570, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China.|Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Qi
authors.affiliation: Research Center for Medicinal Biotechnology, Shandong Academy of Medicinal Sciences, Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology, Binzhou People's Hospital, Binzhou, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Naidong
authors.initials: N
authors.lastname: Xing
authors.affiliation: Department of Human Biology, University of Toronto, Toronto, Canada.
authors.forename: Ran
authors.initials: R
authors.lastname: Du
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China. boh@sdu.edu.cn.|Department of Pathology, Qilu Hospital of Shandong University, Jinan, China. boh@sdu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Han
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D060787:Neoplasm Grading; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D055751:SOXC Transcription Factors / Q000032:analysis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D015854:Up-Regulation
chemical_list: C547077:MIRN132 microRNA, human; C551411:MIRN212 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D016212:Transforming Growth Factor beta
keywords: MiR-132; MiR-212; SOX4; epithelial-mesenchymal transition; prostate cancer