Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a,-224,-132 and let7g
Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a,-224,-132 and let7g
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DOI：
10.1016/j.radonc.2013.06.032
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发表时间：
2013-09-01
影响因子：
5.7
通讯作者：
Gaedcke, Jochen
中科院分区：
文献类型：
--
作者：
Salendo, Junius;Spitzner, Melanie;Gaedcke, Jochen
背景和目的：术前放化疗（CRT）是局部晚期直肠癌的标准治疗。肿瘤缓解和进展差异很大。microRNA代表主调节基因表达，因此可能有助于这种多样性。材料和方法：全基因组microRNA（miRNA）分析进行了12个结直肠癌（CRC）细胞系和一个人在体外签名的chemoradiosensitivity建立。通过将miRNA模拟物转染到SW 480和SW 837细胞中来建立所选miRNA的功能相关性。结果：筛选出36种与CRT敏感性显著相关的miRNAs（Q < 0.05），包括miR-320 a和其他参与MAPK-、TGF-和Wnt-通路的miRNAs。转染选定的miRNA（let-7 g、miR-132、miR-224、miR-320 a）各自诱导敏感性的转变。let-7 g的高表达与直肠癌患者的良好预后相关（P = 0.03）。结论：这是首次报道细胞系体外放化疗敏感性的miRNA表达特征。许多已鉴定的miRNA与CRT的反应无关，可能代表了敏感耐药癌症的潜在分子靶点。如果进一步验证，let 7 g表达可以作为预测生物标志物。(C)2013爱思唯尔爱尔兰有限公司版权所有。放射治疗和肿瘤学108（2013）451-457
Background and purpose: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity.Material and methods: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies.Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7g was associated with a good prognosis in rectal cancer patients (P = 0.03).Conclusions: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 451-457