Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville, Louisville, KY.
Department of Surgery, North Cumbria University Hospitals NHS Trust, Whitehaven, Cumbria, United Kingdom.
Int J Cancer. 2018 Jun 15;142(12):2501-2511. doi: 10.1002/ijc.31282. Epub 2018 Feb 21.
Colorectal cancer (CRC) is associated with significant morbidity and mortality as many patients are diagnosed with advanced stage disease. MicroRNAs are small, noncoding RNA molecules that have a major role in gene expression regulation and are dysregulated in CRC. The miR-200 family is involved in epithelial-mesenchymal transition (EMT). This systematic review describes the roles of the miR-200 family in EMT in CRC. A search of electronic databases (PubMed and Embase) was conducted between January 2000 and July 2017. Both in vitro and human studies reporting on the miR-200 family and CRC were included. Studies describing molecular pathways and the role of the miR-200 family in the diagnostic and therapeutic management of CRC were analyzed. Thirty-four studies (22 in vitro and 18 human studies) were included. miR-200 family expression is regulated epigenetically and via transcriptional factor regulation. In vitro studies show that transfection of miR-200 family members into chemo-resistant colon cancer cell lines results in improved chemo-sensitivity and epithelial phenotype restoration. There is intra-tumoral variability in the tissue expression of miR-200 family members with decreased expression at the invasive front. Clinical studies in CRC patients have shown decreased primary tumor tissue expression of miR-429, miR-200a and miR-200c may be associated with worse survival. Conversely, increased blood levels of miR-141, miR-200a and miR-200c may be associated with worse outcomes. The miR-200 family has a central role in EMT. The miR200 family has potential for both prognostic and therapeutic management of CRC.
结直肠癌（CRC）与显著的发病率和死亡率相关，因为许多患者被诊断为晚期疾病。微小 RNA 是一种小的非编码 RNA 分子，在基因表达调控中起着重要作用，在 CRC 中失调。miR-200 家族参与上皮-间充质转化（EMT）。本系统综述描述了 miR-200 家族在 CRC 中 EMT 中的作用。对 2000 年 1 月至 2017 年 7 月期间的电子数据库（PubMed 和 Embase）进行了搜索。纳入了报告 miR-200 家族和 CRC 的体外和人体研究。分析了描述分子途径和 miR-200 家族在 CRC 的诊断和治疗管理中的作用的研究。纳入了 34 项研究（22 项体外研究和 18 项人体研究）。miR-200 家族的表达受表观遗传和转录因子调节。体外研究表明，将 miR-200 家族成员转染至化疗耐药的结肠癌细胞系中可提高化疗敏感性并恢复上皮表型。miR-200 家族成员在肿瘤组织中的表达存在肿瘤内变异性，在侵袭前沿表达降低。CRC 患者的临床研究表明，初级肿瘤组织中 miR-429、miR-200a 和 miR-200c 的表达降低可能与生存率降低相关。相反，血液中 miR-141、miR-200a 和 miR-200c 的水平升高可能与不良预后相关。miR-200 家族在 EMT 中起核心作用。miR200 家族在 CRC 的预后和治疗管理方面具有潜在作用。
