Overexpression of miR-145–5p Inhibits Proliferation of Prostate Cancer Cells and Reduces SOX2 Expression

ABSTRACT We aimed to perform functional analysis of miR-145–5p in prostate cancer (PCa) cells and to identify targets of miR-145–5p for understanding its role in PCa pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines were utilized for functional analysis of miR-145–5p. Its overexpression caused inhibition of proliferation through apoptosis and reduced migration in PCa cells. SOX2 expression was significantly decreased in both mRNA and protein level in miR-145–5p-overexpressed PCa cells. We proposed that miR-145–5p, being an important regulator of SOX2, carries a crucial role in PCa tumorigenesis.

[1]  M. B. Duz,et al.  The role of miRNAs in cancer: from pathogenesis to therapeutic implications. , 2014, Future oncology.

[2]  N. Seki,et al.  The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer , 2013, Journal of Human Genetics.

[3]  R. Xiang,et al.  SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell. , 2011, Journal of molecular cell biology.

[4]  S. Kakar,et al.  MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. , 2011, Carcinogenesis.

[5]  N. Seki,et al.  Restoration of miR-145 expression suppresses cell proliferation, migration and invasion in prostate cancer by targeting FSCN1. , 2011, International journal of oncology.

[6]  Rajvir Dahiya,et al.  MicroRNA‐205–directed transcriptional activation of tumor suppressor genes in prostate cancer , 2010, Cancer.

[7]  Qunshu Zhang,et al.  Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells , 2010, Cell Death and Disease.

[8]  M. Ittmann,et al.  The function of microRNAs, small but potent molecules, in human prostate cancer , 2010, Prostate Cancer and Prostatic Diseases.

[9]  R. Dahiya,et al.  The functional significance of microRNA-145 in prostate cancer , 2010, British Journal of Cancer.

[10]  D. Steindler,et al.  Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells. , 2010, The Journal of urology.

[11]  Jing Gong,et al.  MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. , 2010, Cancer research.

[12]  S. Griffiths-Jones,et al.  miRBase: microRNA Sequences and Annotation , 2010, Current protocols in bioinformatics.

[13]  J. Cerhan,et al.  Gene networks and microRNAs implicated in aggressive prostate cancer. , 2009, Cancer research.

[14]  I. Gorlov,et al.  Housekeeping genes in prostate tumorigenesis , 2009, International journal of cancer.

[15]  Y. Toiyama,et al.  Correlation of CD133, OCT4, and SOX2 in Rectal Cancer and Their Association with Distant Recurrence After Chemoradiotherapy , 2009, Annals of Surgical Oncology.

[16]  G. Pan,et al.  MicroRNA-145 Regulates OCT4, SOX2, and KLF4 and Represses Pluripotency in Human Embryonic Stem Cells , 2009, Cell.

[17]  Tongbin Li,et al.  miRecords: an integrated resource for microRNA–target interactions , 2008, Nucleic Acids Res..

[18]  Martin Reczko,et al.  The database of experimentally supported targets: a functional update of TarBase , 2008, Nucleic Acids Res..

[19]  Gang Wang,et al.  Crosstalk between the androgen receptor and beta-catenin in castrate-resistant prostate cancer. , 2008, Cancer research.

[20]  C. Tepper,et al.  microRNAs and prostate cancer , 2008, Journal of cellular and molecular medicine.

[21]  A. Swain,et al.  The role of Sox9 in prostate development. , 2008, Differentiation; research in biological diversity.

[22]  Jing Liang,et al.  The Molecular Mechanism Governing the Oncogenic Potential of SOX2 in Breast Cancer* , 2008, Journal of Biological Chemistry.

[23]  Xiaowei Wang miRDB: a microRNA target prediction and functional annotation database with a wiki interface. , 2008, RNA.

[24]  C. Creighton,et al.  Widespread deregulation of microRNA expression in human prostate cancer , 2008, Oncogene.

[25]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[26]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[27]  S. Kasper Exploring the Origins of the Normal Prostate and Prostate Cancer Stem Cell , 2008, Stem Cell Reviews.

[28]  T. Tammela,et al.  MicroRNA expression profiling in prostate cancer. , 2007, Cancer research.

[29]  R. Agami,et al.  Classifying microRNAs in cancer: the good, the bad and the ugly. , 2007, Biochimica et biophysica acta.

[30]  Jialing Yuan,et al.  Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. , 2007, Cancer research.

[31]  M. Becich,et al.  Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process , 2007, BMC Cancer.

[32]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[33]  C. Croce,et al.  MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. Novitch,et al.  Vertebrate neurogenesis is counteracted by Sox1–3 activity , 2003, Nature Neuroscience.

[35]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[36]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.