Genomic Medicine Research Group, Biomedical Sciences Research Institute, Ulster University, Coleraine, UK.
Cancer Biology & Therapeutics Laboratory, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland.
J Cell Physiol. 2020 Sep;235(9):6194-6203. doi: 10.1002/jcp.29548. Epub 2020 Jan 24.
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.
前列腺肿瘤中的缺氧与疾病进展和转移有关。miRNAs 是短的非编码 RNA 分子，在几个细胞过程中非常重要，但它们在缺氧信号中的作用仍知之甚少。miR-210 与缺氧机制有关，但在前列腺癌中其关系尚未得到充分描述。在本报告中，研究了前列腺癌细胞中缺氧与 miR-210 之间的联系。聚合酶链反应分析表明，miR-210 在体外细胞模型和体内前列腺肿瘤异种移植模型中由缺氧诱导。对癌症基因组图谱前列腺活检数据集的分析表明，miR-210 与 Gleason 分级和前列腺癌进展的其他临床标志物显著相关。神经细胞黏附分子（NCAM）被鉴定为 miR-210 的靶标，为缺氧诱导的 miR-210 表达如何有助于前列腺癌提供了生物学机制。本研究提供了证据表明 miR-210 是细胞对缺氧应激反应的重要调节因子，并提出其对 NCAM 的调节可能在前列腺癌的发病机制中发挥重要作用。
