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Int J Oncol. 2012 May;40(5):1553-60. doi: 10.3892/ijo.2012.1342. Epub 2012 Jan 24.

miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer.

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  • 1Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, PR China.

Abstract

MicroRNAs play critical roles in tumorigenesis as either oncogenes or tumor suppressors. As a microRNA induced by Twist, miR-10b function as a metastasis driver in different types of cancer, in which the downstream target gene HOXD10 is the main mediator. In gastric tumor species, miR-10b levels were dramatically elevated in lymphoma node metastasis-positive tumor tissues compared with lymphoma node metastasis-free tumor tissues, and were correlated to dowregulation of HOXD10 expression. In gastric cell lines with distinct degrees of differentiation, miR-10b was highly expressed in the cell line with strong metastatic ability. In MNK45 cells, inhibition of miR-10b led to abrogation of cell invasion. While in GES-1 cells, miR-10 overexpression resulted in enhancement of invasiveness through translational inhibition of HOXD10, and constitutive expression of HOXD10 reversed the effects of miR-10b on cell invasion. Furthermore, either knockdown of RhoC or inhibition of AKT activation interfered miR-10-induced invasiveness in GES-1 cells. In summary, these observations suggest that miR-10b can stimulate the upregulation of RhoC and AKT phosphorylation through targeting HOXD10, thus promoting cell invasion in gastric tumors.

PMID:
22293682
[PubMed - indexed for MEDLINE]
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