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Cell Death Dis. 2014 Jul 17;5:e1335. doi: 10.1038/cddis.2014.304.

miR-29b suppresses tumor growth and metastasis in colorectal cancer via downregulating Tiam1 expression and inhibiting epithelial-mesenchymal transition.

Author information

  • 1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • 4Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China.
  • 51] Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China [2] Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Abstract

Recently, the role of miR-29b in colorectal carcinoma (CRC) development appears to be controversial. Until now, the expression and function of miR-29b in CRC have not been clarified clearly. We showed that decreased expression of miR-29b usually occurred in CRC cell lines and tissue samples. Loss- and gain-of-function assays in vitro revealed suppressive effects of miR-29b on cell proliferation and migration. Endogenous overexpression of miR-29b was sufficient to suppress aggressive behavioral phenotypes in mice. Proteomic analysis showed that miR-29b involved in integrate several key biological processes. In addition, miR-29b mediated the inhibition of epithelial-mesenchymal transition (EMT) and the inactivation of mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT signal transduction pathway. Further studies found that T lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct target of miR-29b. In contrast to the phenotypes induced by miR-29b restoration, Tiam1-induced cell proliferation and migration partly rescued miR-29b-mediated biological behaviors. Our results illustrated that miR-29b as a suppressor has a critical role in CRC progression, which suggests its potential role in the molecular therapy of patients with advanced CRC.

PMID:
25032858
[PubMed - in process]
PMCID:
PMC4123095
Free PMC Article

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