Portal de Periódicos da CAPES

microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer

2018; American Association for Cancer Research; Volume: 78; Issue: 7 Linguagem: Inglês

10.1158/0008-5472.can-17-2069

1538-7445

Divya Bhagirath, Thao Ly Yang, Nathan Bucay, Kirandeep Sekhon, Shahana Majid, Varahram Shahryari, Rajvir Dahiya, Yuichiro Tanaka, Sharanjot Saini,

Circular RNAs in diseases

Abstract Because of high heterogeneity, molecular characterization of prostate cancer based on biopsy sampling is often challenging. Hence, a minimally invasive method to determine the molecular imprints of a patient's tumor for risk stratification would be advantageous. In this study, we employ a novel, digital amplification-free quantification method using the nCounter technology (NanoString Technologies) to profile exosomal serum miRNAs (ex-miRNA) from aggressive prostate cancer cases, benign prostatic hyperplasia, and disease-free controls. We identified several dysregulated miRNAs, one of which was the tumor suppressor miR-1246. miR-1246 was downregulated in prostate cancer clinical tissues and cell lines and was selectively released into exosomes. Overexpression of miR-1246 in a prostate cancer cell line significantly inhibited xenograft tumor growth in vivo and increased apoptosis and decreased proliferation, invasiveness, and migration in vitro. miR-1246 inhibited N-cadherin and vimentin activities, thereby inhibiting epithelial–mesenchymal transition. Ex-miR-1246 expression correlated with increasing pathologic grade, positive metastasis, and poor prognosis. Our analyses suggest ex-miR-1246 as a promising prostate cancer biomarker with diagnostic potential that can predict disease aggressiveness. Significance: Dysregulation of exosomal miRNAs in aggressive prostate cancer leads to alteration of key signaling pathways associated with metastatic prostate cancer. Cancer Res; 78(7); 1833–44. ©2018 AACR.