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      Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA-MUF Interaction with ANXA2 and miR-34a.

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          Abstract

          Accumulating evidence suggests that cancer-associated mesenchymal stem cells (MSC) contribute to the development and metastasis of hepatocellular carcinoma (HCC). Aberrant expression of long noncoding RNAs (lncRNA) has been associated with these processes but cellular mechanisms are obscure. In this study, we report that HCC-associated mesenchymal stem cells (HCC-MSC) promote epithelial-mesenchymal transition (EMT) and liver tumorigenesis. We identified a novel lncRNA that we termed lncRNA-MUF (MSC-upregulated factor) that is highly expressed in HCC tissues and correlated with poor prognosis. Depleting lncRNA-MUF in HCC cells repressed EMT and inhibited their tumorigenic potential. Conversely, lncRNA-MUF overexpression accelerated EMT and malignant capacity. Mechanistic investigations showed that lncRNA-MUF bound Annexin A2 (ANXA2) and activated Wnt/β-catenin signaling and EMT. Furthermore, lncRNA-MUF acted as a competing endogenous RNA for miR-34a, leading to Snail1 upregulation and EMT activation. Collectively, our findings establish a lncRNA-mediated process in MSC that facilitates hepatocarcinogenesis, with potential implications for therapeutic targeting. Cancer Res; 77(23); 6704-16. ©2017 AACR.

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          Author and article information

          Journal
          Cancer Res.
          Cancer research
          American Association for Cancer Research (AACR)
          1538-7445
          0008-5472
          Dec 01 2017
          : 77
          : 23
          Affiliations
          [1 ] College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China. yxlong2000@bjut.edu.cn rschen@sun5.ibp.ac.cn fanz@moon.ibp.ac.cn.
          [2 ] Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
          [3 ] Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
          [4 ] Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
          [5 ] University of Chinese Academy of Sciences, Beijing, China.
          [6 ] Department of Tissue Engineering, Beijing Institute of Transfusion Medicine, Beijing, China.
          [7 ] College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.
          [8 ] Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. yxlong2000@bjut.edu.cn rschen@sun5.ibp.ac.cn fanz@moon.ibp.ac.cn.
          [9 ] Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. yxlong2000@bjut.edu.cn rschen@sun5.ibp.ac.cn fanz@moon.ibp.ac.cn.
          Article
          0008-5472.CAN-17-1915
          10.1158/0008-5472.CAN-17-1915
          28947421

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