miR‐210 is induced by hypoxia and regulates neural cell adhesion molecule in prostate cells

• Published in: Journal of cellular physiology Vol. 235; no. 9; pp. 6194 - 6203
• Main Authors: Angel, Charlotte Zoe, Lynch, Seodhna M., Nesbitt, Heather, McKenna, Michael M., Walsh, Colum P., McKenna, Declan J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2020
• Subjects: Adhesion; Animals; Biopsy; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell culture; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic - genetics; Genomes; Heterografts; Humans; Hypoxia; Male; Metastases; Mice; microRNA; MicroRNAs - genetics; miRNA; miR‐210; NCAM; Neural cell adhesion molecule; Neural Cell Adhesion Molecules - genetics; Pathogenesis; Polymerase chain reaction; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Signal Transduction - genetics; Target recognition; Tumor Hypoxia - genetics; Tumors; Xenografts; Xenotransplantation; hypoxia; microRNA; prostate cancer; NCAM; miR-210
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29548

Hypoxia in prostate tumours has been associated with disease progression and metastasis. MicroRNAs are short noncoding RNA molecules that are important in several cell processes, but their role in hypoxic signalling is still poorly understood. miR‐210 has been linked with hypoxic mechanisms, but this relationship has been poorly characterised in prostate cancer. In this report, the link between hypoxia and miR‐210 in prostate cancer cells is investigated. Polymerase chain reaction analysis demonstrates that miR‐210 is induced by hypoxia in prostate cancer cells using in vitro cell models and an in vivo prostate tumour xenograft model. Analysis of The Cancer Genome Atlas prostate biopsy datasets shows that miR‐210 is significantly correlated with Gleason grade and other clinical markers of prostate cancer progression. Neural cell adhesion molecule (NCAM) is identified as a target of miR‐210, providing a biological mechanism whereby hypoxia‐induced miR‐210 expression can contribute to prostate cancer. This study provides evidence that miR‐210 is an important regulator of cell response to hypoxic stress and proposes that its regulation of NCAM may play an important role in the pathogenesis of prostate cancer. This is the first study to show that hypoxia‐induced expression of miR‐210 in prostate cells regulates neural cell adhesion molecule expression. The data shows that miR‐210 is significantly upregulated by hypoxia in prostate cells in vitro and in vivo, as well as demonstrating that miR‐210 expression is positively correlated with tumour aggressiveness in human prostate cancer tissue. This study provides evidence for the use of miR‐210 as a diagnostic or prognostic marker in prostate cancer, and may also be a potential target for therapeutic intervention.