miR-155-5p inhibition promotes the transition of bone marrow mesenchymal stem cells to gastric cancer tissue derived MSC-like cells via NF-κB p65 activation

作者：Mengchu Zhu, Mei Wang, Fang Yang, Yiqing Tian, Jie Cai, Huan Yang, Hailong Fu, Fei Mao, Wei Zhu, Hui Qian, Wenrong Xu · 发表于：Oncotarget · 年份：2016 · DOI：10.18632/oncotarget.7767 · 被引用次数：71 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、Circular RNAs in diseases

// Mengchu Zhu 1,* , Mei Wang 1,* , Fang Yang 1 , Yiqing Tian 1 , Jie Cai 1 , Huan Yang 1 , Hailong Fu 1 , Fei Mao 1 , Wei Zhu 1 , Hui Qian 1 and Wenrong Xu 1 1 Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China * These authors have contributed equally to this work Correspondence to: Mei Wang, email: // Wenrong Xu, email: // Keywords : mesenchymal stem cells, gastric cancer, microRNA, tumor microenvironment Received : August 06, 2015 Accepted : February 05, 2016 Published : February 26, 2016 Abstract Gastric cancer tissue-derived MSC-like cells (GC-MSC) share similar characteristics to bone marrow MSC (BM-MSC); however, the phenotypical and functional differences and the molecular mechanism of transition between the two cell types remain unclear. Compared to BM-MSC, GC-MSC exhibited the classic phenotype of reactive stroma cells, a stronger gastric cancer promoting capacity and lower expression of miR-155-5p. Inhibition of miR-155-5p by transfecting miRNA inhibitor induced a phenotypical and functional transition of BM-MSC into GC-MSC-like cells, and the reverse experiment deprived GC-MSC of tumor-promoting phenotype and function. NF-kappa B p65 (NF-κB p65) and inhibitor of NF-kappa B kinase subunit epsilon (IKBKE/IKKε) were identified as targets of miR-155-5p and important for miRNA inhibitor activating NF-κB p65 in the transition. Inactivation of NF-κB by ...