Sun Yifeng, Chen Chang, Zhang Peng, Xie Huikang, Hou Likun, Hui Zheng, Xu Yongjie, Du Qiaoling, Zhou Xiao, Su Bo, Gao Wen
1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2] Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated Shanghai Jiaotong University, No. 241, Huaihaixi Road, Shanghai, 200030, P.R. China [3].
1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2].
Sci Rep. 2014 Oct 6;4:6527. doi: 10.1038/srep06527.
miR-3127-5p is a primate-specific miRNA which is down-regulated in recurrent NSCLC tissue vs. matched primary tumor tissue (N = 15) and in tumor tissue vs. normal lung tissue (N = 177). Reduced miR-3127-5p expression is associated with a higher Ki-67 proliferation index and unfavorable prognosis in NSCLC. Overexpression of miR-3127-5p significantly reduced NSCLC cells proliferation, migration, and motility in vitro and in vivo. The oncogene ABL1 was a direct miR-3127-5p target, and miR-3127-5p regulated the activation of the Abl/Ras/ERK pathway and transactivated downstream proliferation/metastasis-associated molecules. Overexpression of miR-3127-5p in A549 or H292 cells resulted in enhanced resistance to dasatinib, an Abl/src tyrosine kinase inhibitor. miR-3127-5p expression levels were correlated with dasatinib sensitivity in NSCLC cell lines without K-Ras G12 mutation. In conclusion, miR-3127-5p acts as a tumor suppressor gene and is a potential biomarker for dasatinib sensitivity in the non-mutated Ras subset of NSCLC.
miR-3127-5p是一种灵长类动物特有的微小RNA，在复发性非小细胞肺癌组织与配对的原发性肿瘤组织（N = 15）以及肿瘤组织与正常肺组织（N = 177）中表达下调。miR-3127-5p表达降低与非小细胞肺癌中较高的Ki-67增殖指数及不良预后相关。miR-3127-5p的过表达在体外和体内均显著降低了非小细胞肺癌细胞的增殖、迁移和运动能力。癌基因ABL1是miR-3127-5p的直接靶点，miR-3127-5p调节Abl/Ras/ERK途径的激活并反式激活下游增殖/转移相关分子。在A549或H292细胞中过表达miR-3127-5p导致对达沙替尼（一种Abl/src酪氨酸激酶抑制剂）的耐药性增强。在无K-Ras G12突变的非小细胞肺癌细胞系中，miR-3127-5p表达水平与达沙替尼敏感性相关。总之，miR-3127-5p作为一种肿瘤抑制基因，是无Ras突变的非小细胞肺癌亚组中达沙替尼敏感性的潜在生物标志物。
