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

• DOI: 10.18632/oncotarget.7767
• Publication Date: 2016-02-27T04:51:15Z
• Authors: Mengchu Zhu; Mei Wang; Fang Yang; Yiqing Tian; Jie Cai; Huan Yang; Hailong Fu; Fei Mao; Wei Zhu; Hui Qian; Wenrong Xu
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Pyrrolidines; Transplantation, Heterologous; Transcription Factor RelA; Down-Regulation; Mice, Nude; Bone Marrow Cells; Mesenchymal Stem Cells; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Transformation, Neoplastic; HEK293 Cells; Stomach Neoplasms; Thiocarbamates; Cell Line, Tumor; Animals; Humans; RNA Interference; 3' Untranslated Regions; Cells, Cultured; Research Paper

// Mengchu Zhu 1,* , Mei Wang Fang Yang 1 Yiqing Tian Jie Cai Huan Hailong Fu Fei Mao Wei Hui Qian and Wenrong Xu Key Laboratory of Medical Science Medicine Jiangsu Province, School Medicine, University, Zhenjiang, Jiangsu, China * These authors have contributed equally to this work Correspondence to: Wang, email: Xu, Keywords : mesenchymal stem cells, gastric cancer, microRNA, tumor microenvironment Received August 06, 2015 Accepted February 05, 2016 Published 26, Abstract Gastric cancer tissue-derived MSC-like cells (GC-MSC) share similar characteristics bone marrow MSC (BM-MSC); however, the phenotypical functional differences molecular mechanism transition between two cell types remain unclear. Compared BM-MSC, GC-MSC exhibited classic phenotype reactive stroma a stronger promoting capacity lower expression miR-155-5p. Inhibition miR-155-5p by transfecting miRNA inhibitor induced BM-MSC into GC-MSC-like reverse experiment deprived tumor-promoting function. NF-kappa B p65 (NF-κB p65) kinase subunit epsilon (IKBKE/IKKε) were identified as targets important for activating NF-κB in transition. Inactivation pyrrolidine dithiocarbamic acid (PDTC) significantly blocked effect on BM-MSC. IKBKE, phospho-NF-κB proteins highly enriched tissues, latter correlated with pathological progression cancer. In GC-MSC, was downregulated protein increased activated. inactivation PDTC or knockdown its downstream cytokines reversed function GC-MSC. Taken together, our findings revealed that downregulation induces acquire depending activation, which suggests novel underlying associated remodeling offers an effective target approach therapy.