Exosomal microRNA profiling to identify hypoxia-related biomarkers in prostate cancer
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Gati K. Panigrahi1,*, Anand Ramteke2,*, Diane Birks3, Hamdy E. Abouzeid Ali4, Sujatha Venkataraman3, Chapla Agarwal3, Rajeev Vibhakar3, Lance D. Miller1,5, Rajesh Agarwal3, Zakaria Y. Abd Elmageed4 and Gagan Deep1,5,6
1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
2Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, India
3University of Colorado Denver, Aurora, Colorado, USA
4Department of Pharmaceutical Sciences, Texas A&M Rangel College of Pharmacy, Kingsville, Texas, USA
5Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina, USA
6Department of Urology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
*These authors contributed equally to this work
Gagan Deep, email: [email protected]
Keywords: prostate cancer; hypoxia; exosomes; miRNAs; biomarkers
Received: November 30, 2017 Accepted: February 10, 2018 Published: February 17, 2018
Hypoxia and expression of hypoxia-related biomarkers are associated with disease progression and treatment failure in prostate cancer (PCa). We have reported that exosomes (nanovesicles of 30-150 nm in diameter) secreted by human PCa cells under hypoxia promote invasiveness and stemness in naïve PCa cells. Here, we identified the unique microRNAs (miRNAs) loaded in exosomes secreted by PCa cells under hypoxia. Using TaqMan® array microRNA cards, we analyzed the miRNA profile in exosomes secreted by human PCa LNCaP cells under hypoxic (ExoHypoxic) and normoxic (ExoNormoxic) conditions. We identified 292 miRNAs loaded in both ExoHypoxic and ExoNormoxic. The top 11 miRNAs with significantly higher level in ExoHypoxic compared to ExoNormoxic were miR-517a, miR-204, miR-885, miR-143, miR-335, miR-127, miR-542, miR-433, miR-451, miR-92a and miR-181a; and top nine miRNA with significantly lower expression level in ExoHypoxic compared to ExoNormoxic were miR-521, miR-27a, miR-324, miR-579, miR-502, miR-222, miR-135b, miR-146a and miR-491. Importantly, the two differentially expressed miRNAs miR-885 (increased expression) and miR-521 (decreased expression) showed similar expression pattern in exosomes isolated from the serum of PCa patients compared to healthy individuals. Additionally, miR-204 and miR-222 displayed correlated expression patterns in prostate tumors (Pearson R = 0.66, p < 0.0001) by The Cancer Genome Atlas (TCGA) prostate adenocarcinoma (PRAD) genomic dataset analysis. Overall, the present study identified unique miRNAs with differential expression in exosomes secreted from hypoxic PCa cells and suggests their potential usefulness as a biomarker of hypoxia in PCa patients.
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