MicroRNA-1246 is an exosomal biomarker for aggressive prostate cancer

Due to high heterogeneity, molecular characterization of prostate cancer (PCa) 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 PCa cases, benign prostatic hyperplasia (BPH), and disease-free controls. We identified several dysregulated miRNAs, one of which was the tumor suppressor miR-1246. miR-1246 was downregulated in PCa clinical tissues and cell lines and was selectively released into exosomes. Overexpression of miR-1246 in a PCa 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 pathological grade, positive metastasis, and poor prognosis. Our analyses suggest ex-miR-1246 as a promising PCa biomarker with diagnostic potential that can predict disease aggressiveness.

Cancer research. 2018 Feb 01 [Epub ahead of print]

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

UCSF and SFVAMC., Urology, UCSF/SFVAMC., Urology, UCSF and SFVAMC., Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco., Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco., Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco .