The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients.
The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients.
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DOI：
10.1371/journal.pone.0173664
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Silver A
中科院分区：
文献类型：
--
作者：
Lewis A;Felice C;Kumagai T;Lai C;Singh K;Jeffery RR;Feakins R;Giannoulatou E;Armuzzi A;Jawad N;Lindsay JO;Silver A
结直肠癌（CRC）是溃疡性结肠炎（UC）的一种危及生命的并发症，患者经常接受癌前病变（不典型增生）的筛查。然而，在不同的研究中，确诊为低级别发育不良的患者的结直肠癌发病率差异很大，这表明这些病变之间存在很大程度的异质性，而这些异质性是无法从宏观上检测到的。更好地了解在发育不良中发生的潜在分子变化将有助于识别恶性肿瘤高风险的病变。MicroRNAs （miRNAs）通过转录后调控蛋白表达和细胞信号网络。异常miRNA表达是散发性结直肠癌的一个特征，但对异常增生和UC中发生的变化知之甚少。对UC发育不良病变（n = 7）和UC对照组（n = 10）提取的RNA进行全面的microRNA谱分析。还评估了UC炎性息肉后mirna的表达（n = 7）。候选miRNA通过qPCR和miRNA原位杂交进一步验证。还评估了血清mirna水平，以确定非侵入性发育不良的生物标志物。UC发育不良与炎性息肉中未见的miRNA表达谱的变化有关。特别是，miR-200b-3p水平在发育不良中升高，并且该miRNA定位于发育不良病变和UC癌症中的上皮细胞。血清中未检测到miRNA水平的变化。uc -不典型增生与粘膜miRNA表达改变和miR-200b-3p水平升高有关。
Colorectal cancer (CRC) is a life-threatening complication of ulcerative colitis (UC), and patients are routinely screened for the development of precancerous lesions (dysplasia). However, rates of CRC development in patients with confirmed low-grade dysplasia vary widely between studies, suggesting a large degree of heterogeneity between these lesions that is not detectable macroscopically. A better understanding of the underlying molecular changes that occur in dysplasia will help to identify lesions at higher risk of malignancy. MicroRNAs (miRNAs) post-transcriptionally regulate protein expression and cell-signalling networks. Aberrant miRNA expression is a feature of sporadic CRC but much less is known about the changes that occur in dysplasia and in UC. Comprehensive microRNA profiling was performed on RNA extracted from UC dysplastic lesions (n = 7) and UC controls (n = 10). The expression of miRNAs in UC post inflammatory polyps (n = 7) was also assessed. Candidate miRNAs were further validated by qPCR, and miRNA in situ hybridization. Serum levels of miRNAs were also assessed with a view to identification of non-invasive biomarkers of dysplasia. UC dysplasia was associated with a shift in miRNA expression profiles that was not seen in inflammatory polyps. In particular, levels of miR-200b-3p were increased in dysplasia, and this miRNA was localised to epithelial cells in dysplastic lesions and in UC cancers. No changes in miRNA levels were detected in the serum. UC-Dysplasia is linked to altered miRNA expression in the mucosa and elevated miR-200b-3p levels.