microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2018-04, Vol.78 (7), p.1833-1844
Main Authors: Bhagirath, Divya, Yang, Thao Ly, Bucay, Nathan, Sekhon, Kirandeep, Majid, Shahana, Shahryari, Varahram, Dahiya, Rajvir, Tanaka, Yuichiro, Saini, Sharanjot
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - genetics
Biomarkers
Biomarkers, Tumor - genetics
Biopsy
Cadherins
Cadherins - metabolism
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Cell Survival - genetics
Epithelial-Mesenchymal Transition - genetics
Exosomes
Exosomes - genetics
Gene Expression Regulation, Neoplastic
Humans
Hyperplasia
Male
Mesenchyme
Metastases
Metastasis
Mice
Mice, Nude
MicroRNAs - genetics
miRNA
N-Cadherin
Neoplasm Transplantation
PC-3 Cells
Prostate - pathology
Prostate cancer
Prostatic Hyperplasia - genetics
Prostatic Hyperplasia - pathology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Signal transduction
Tissues
Transplantation, Heterologous
Tumor cell lines
Tumor suppressor genes
Vimentin
Vimentin - metabolism
Xenografts
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Summary: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 and increased apoptosis and decreased proliferation, invasiveness, and migration 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. Dysregulation of exosomal miRNAs in aggressive prostate cancer leads to alteration of key signaling pathways associated with metastatic prostate cancer. .
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-17-2069