Histone methyltransferase PRMT6 plays an oncogenic role of in prostate cancer.
Prostate cancer (PCa) is a major cause of morbidity and mortality. Until now the specific role of histone methyltransferases (HMTs) deregulated expression/activity in PCa is poorly understood. Herein we aimed to uncover the potential oncogenic role of PRMT6 in prostate carcinogenesis. PRMT6 overexpression was confirmed in PCa, at transcript and protein level. Stable PRMT6 knockdown in PC-3 cells attenuated malignant phenotype, increasing apoptosis and decreasing cell viability, migration and invasion. PRMT6 silencing was associated with decreased H3R2me2a levels and increased MLL and SMYD3 expression. PRMT6 silencing increased p21, p27 and CD44 and decreased MMP-9 expression and was associated with PI3K/AKT/mTOR downregulation and increased AR signaling pathway. In Sh-PRMT6 cells, AR restored expression might re-sensitized cells to androgen deprivation therapy, impacting in clinical management of castration-resistant PCa (CRPC). PRMT6 plays an oncogenic role in PCa and predicts for more clinically aggressive disease, constituting a potential target for patients with CRPC.
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.
Diogo
D
Almeida-Rios
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Morphological Sciences, School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Porto, Portugal.
Inês
I
Graça
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Morphological Sciences, School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Porto, Portugal.
Filipa Quintela
FQ
Vieira
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.
João
J
Ramalho-Carvalho
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.
Eva
E
Pereira-Silva
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.
Ana Teresa
AT
Martins
Department of Urology, Portuguese Oncology Institute of Porto, Porto, Portugal.
Jorge
J
Oliveira
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's PT Government Associate Laboratory, Braga/Guimarães, Braga, Portugal.
Céline S
CS
Gonçalves
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's PT Government Associate Laboratory, Braga/Guimarães, Braga, Portugal.
Bruno M
BM
Costa
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Rui
R
Henrique
Cancer Biology & Epigenetics Group Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Carmen
C
Jerónimo
D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D009687:Nuclear Proteins; D011944:Receptors, Androgen; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases; D020780:Matrix Metalloproteinase 9
PRMT6; androgen receptor; histone methyltransferase; prostate cancer