title: miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110.
abstract: 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.
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Irene V
authors.initials: IV
authors.lastname: Bijnsdorp
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Hodzic
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tonny
authors.initials: T
authors.lastname: Lagerweij
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Westerman
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Oscar
authors.initials: O
authors.lastname: Krijgsman
authors.affiliation: Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands.
authors.forename: Jurjen
authors.initials: J
authors.lastname: Broeke
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Verweij
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.|Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: R Jonas A
authors.initials: RJ
authors.lastname: Nilsson
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rozendaal
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Victor W
authors.initials: VW
authors.lastname: van Beusechem
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen A
authors.initials: JA
authors.lastname: van Moorselaar
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.|Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wurdinger
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Geldof
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats
chemical_list: C467559:CCP110 protein, human; D018797:Cell Cycle Proteins; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C541915:Mirn129 microRNA, human; D010750:Phosphoproteins
keywords: CP110; centrosome; metastasis; miR-129-3p; prostate cancer