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      MicroRNA-187, a downstream effector of TGFβ pathway, suppresses Smad-mediated epithelial-mesenchymal transition in colorectal cancer.

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          Abstract

          Constitutive overactivation of TGFβ signaling is a common event in human cancer progression and acts as a major inducer of epithelial-mesenchymal transition (EMT). In pre-metastatic colorectal cancer (CRC) cells, however, this cascade is tightly controlled and the underlying mechanism in TGFβ stimulated hyperactivation of downstream Smad pathway remains elusive. In this study, expression of miR-187 was downregulated in colorectal cancer (CRC) compared with adjacent normal tissues. miR-187 could suppress the formation of aggressive phenotype in CRC and inactivate Smad pathway, thus preventing EMT. TGFβ stimulation significantly suppressed the expression of miR-187, and overexpressed miR-187 counteracted the influence of TGFβ on cell phenotype and downstream pathway. Furthermore, we found that miR-187 directly suppressed the expression of SOX4, NT5E and PTK6, which were identified as essential upstream effectors of Smad pathway. Together with the fact that high SOX4 or NT5E levels were associated with poor prognosis, we also demonstrated that downregulation of miR-187 was closely related to tumor metastasis and poor prognosis in CRC. These findings revealed a plausible mechanism for sustained TGFβ activation in cancer progression and might have suggested a novel miR-187-based clinical intervention target for patients with advanced CRC.

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          Author and article information

          Journal
          Cancer Lett.
          Cancer letters
          1872-7980
          0304-3835
          Apr 10 2016
          : 373
          : 2
          Affiliations
          [1 ] Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
          [2 ] Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
          [3 ] The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
          [4 ] Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
          [5 ] Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
          [6 ] Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. Electronic address: liangsmu@foxmail.com.
          Article
          S0304-3835(16)30007-6
          10.1016/j.canlet.2016.01.037
          26820227
          dd0b79a0-7625-4eda-bd95-af1cbfba9b68
          Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
          History

          Colorectal carcinoma,Epithelial–mesenchymal transition,Transforming growth factor beta,Tumor metastasis,microRNA-187

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