miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110

The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.

[1]  O. Kucuk,et al.  How to be good at being bad: centrosome amplification and mitotic propensity drive intratumoral heterogeneity , 2015, Cancer and Metastasis Reviews.

[2]  M. Larocca,et al.  Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization of the centrosome and Golgi in migratory cells , 2015, Journal of Cell Science.

[3]  M. Malumbres,et al.  Aurora kinase A inhibitors: promising agents in antitumoral therapy , 2014, Expert opinion on therapeutic targets.

[4]  John Calvin Reed,et al.  PCTAIRE1 phosphorylates p27 and regulates mitosis in cancer cells. , 2014, Cancer research.

[5]  M. Moussa,et al.  SKA1 over‐expression promotes centriole over‐duplication, centrosome amplification and prostate tumourigenesis , 2014, The Journal of pathology.

[6]  B. Ylstra,et al.  Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. , 2014, Cell reports.

[7]  S. Rogers,et al.  Excess centrosomes disrupt endothelial cell migration via centrosome scattering , 2014, The Journal of cell biology.

[8]  Lin He,et al.  miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110 , 2014, Nature.

[9]  J. Deursen,et al.  Cyclin B2 and p53 control proper timing of centrosome separation , 2014, Nature Cell Biology.

[10]  K. Polyak,et al.  Oncogene-like induction of cellular invasion from centrosome amplification , 2014, Nature.

[11]  Samy Lamouille,et al.  Molecular mechanisms of epithelial–mesenchymal transition , 2014, Nature Reviews Molecular Cell Biology.

[12]  T. Ziegler,et al.  Steroidogenic factor 1 promotes aggressive growth of castration-resistant prostate cancer cells by stimulating steroid synthesis and cell proliferation. , 2014, Endocrinology.

[13]  J. Raff,et al.  CP110 exhibits novel regulatory activities during centriole assembly in Drosophila , 2013, The Journal of cell biology.

[14]  S. Kuang,et al.  Plk1‐dependent microtubule dynamics promotes androgen receptor signaling in prostate cancer , 2013, The Prostate.

[15]  Shiaoching Gong,et al.  Current mouse and cell models in prostate cancer research. , 2013, Endocrine-Related Cancer.

[16]  R. Nagle,et al.  Primary Cilia Are Lost in Preinvasive and Invasive Prostate Cancer , 2013, PloS one.

[17]  Anirban P. Mitra,et al.  Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy , 2013, PloS one.

[18]  M. Pagano,et al.  USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110 , 2013, Nature.

[19]  G. Berx,et al.  Regulatory networks defining EMT during cancer initiation and progression , 2013, Nature Reviews Cancer.

[20]  S. Duensing,et al.  The centrosome as potential target for cancer therapy and prevention , 2013, Expert opinion on therapeutic targets.

[21]  R. Medema,et al.  Switching Polo-like kinase-1 on and off in time and space. , 2012, Trends in biochemical sciences.

[22]  A. Geldof,et al.  A predictive role for noncancerous prostate cells: low connexin-26 expression in radical prostatectomy tissues predicts metastasis , 2012, British Journal of Cancer.

[23]  M. Rubin,et al.  Genome-wide DNA methylation events in TMPRSS2-ERG fusion-negative prostate cancers implicate an EZH2-dependent mechanism with miR-26a hypermethylation. , 2012, Cancer discovery.

[24]  M. Piel,et al.  Never tear us apart – the importance of centrosome clustering , 2012, Journal of Cell Science.

[25]  Xiumin Yan,et al.  miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics , 2012, Nature Cell Biology.

[26]  T. Visakorpi,et al.  Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer , 2012, Oncogene.

[27]  S. Lowe,et al.  The microcosmos of cancer , 2012, Nature.

[28]  J. Chan.  A Clinical Overview of Centrosome Amplification in Human Cancers , 2011, International journal of biological sciences.

[29]  M. Schuler,et al.  Polo-like kinase 1 inhibitors in mono- and combination therapies: a new strategy for treating malignancies , 2011, Expert review of anticancer therapy.

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

[31]  H. Nojima,et al.  GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression , 2009, Journal of Cell Science.

[32]  G. Kristiansen,et al.  Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma , 2009, International journal of cancer.

[33]  F. Gergely,et al.  Centrosome function in cancer: guilty or innocent? , 2009, Trends in cell biology.

[34]  David Pellman,et al.  A Mechanism Linking Extra Centrosomes to Chromosomal Instability , 2009, Nature.

[35]  S. Varambally,et al.  Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer , 2008, Science.

[36]  Eric C. Lai,et al.  Biological principles of microRNA-mediated regulation: shared themes amid diversity , 2008, Nature Reviews Genetics.

[37]  Jack Y. Yang,et al.  Transcription factor and microRNA regulation in androgen-dependent and -independent prostate cancer cells , 2008, BMC Genomics.

[38]  Robyn L Prueitt,et al.  Tumor immunobiological differences in prostate cancer between African-American and European-American men. , 2008, Cancer research.

[39]  Ralph Weissleder,et al.  A secreted luciferase for ex vivo monitoring of in vivo processes , 2008, Nature Methods.

[40]  David M. Glover,et al.  Centrosome biogenesis and function: centrosomics brings new understanding , 2007, Nature Reviews Molecular Cell Biology.

[41]  Harry Vrieling,et al.  Analysis of Gene Expression Using Gene Sets Discriminates Cancer Patients with and without Late Radiation Toxicity , 2006, PLoS medicine.

[42]  Brian David Dynlacht,et al.  CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. , 2006, Molecular biology of the cell.

[43]  G. Sluder,et al.  The good, the bad and the ugly: the practical consequences of centrosome amplification. , 2004, Current opinion in cell biology.

[44]  I. Fidler,et al.  The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited , 2003, Nature Reviews Cancer.

[45]  S. Tsao,et al.  Effect of p53 on centrosome amplification in prostate cancer cells. , 2001, Biochimica et biophysica acta.

[46]  M. Sokoloff,et al.  The Dunning model , 2000, The Prostate.

[47]  A. Geldof,et al.  Radionuclide therapy for prostate cancer lumbar metastasis prolongs symptom-free survival in a rat model. , 1997, Urology.

[48]  E. Moore.  Cáncer , 1939, Atenea (Concepción).

[49]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[50]  M. Pagano,et al.  SCFCyclin F controls centrosome homeostasis and mitotic fidelity through CP 110 degradation , 2010 .

[51]  S. Dedhar,et al.  Specific alterations in the expression of alpha 3 beta 1 and alpha 6 beta 4 integrins in highly invasive and metastatic variants of human prostate carcinoma cells selected by in vitro invasion through reconstituted basement membrane. , 1993, Clinical & experimental metastasis.

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