microRNA-1246 is an exosomal biomarker for aggressive prostate cancer

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

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1833-1844
Number of pages12
JournalCancer Research
Volume78
Issue number7
DOIs
StatePublished - Apr 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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