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Oncotarget. 2016 Sep 13;7(37):60230-60244. doi: 10.18632/oncotarget.11176.

MicroRNA-126 inhibits colon cancer cell proliferation and invasion by targeting the chemokine (C-X-C motif) receptor 4 and Ras homolog gene family, member A, signaling pathway.

Yuan W1,2, Guo YQ1,3, Li XY1,2, Deng MZ1,2, Shen ZH1,2, Bo CB1,2, Dai YF4, Huang MY1,2, Yang ZY1,2, Quan YS1,2, Tian L1,2, Wang X1,2.

Author information

1
Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
2
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
3
Department of Gastroenterology, Yichang Central People's Hospital, Yichang, Hubei, China.
4
Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, China.

Abstract

MicroRNA-126 (miR-126) suppresses the migration, proliferation and invasion of colon cancer cells. However, the underlying mechanisms of miR-126 in colon cancer have not been fully elucidated. In this study, in vivo experiments revealed that miR-126 inhibits colon cancer growth and metastasis. Furthermore, miR-126 was down-regulated in human colon cancer tissue, and its expression was inversely correlated with TNM stage and metastasis of patients. Low level of miR-126 identified patients with poor prognosis. And we found that miR-126 expression was negatively correlated with the expression levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and components of signaling pathway of Ras homolog gene family, member A (RhoA) in vitro and in vivo. Moreover, we verified that miR-126 negatively regulated CXCR4 and RhoA signaling in vitro. In addition, either in miR-126-overexpressing or in miR- 126-silenced colon cancer cells, the restoration of CXCR4 could significantly reverse the proliferation and invasion, as well as abolish the effects of miR-126 on RhoA signaling pathway. Collectively, these results demonstrated that miR-126 acts as a tumor suppressor by inactivating RhoA signaling via CXCR4 in colon cancer. And miR-126 may serve as a prognostic marker for monitoring and treating colon cancer.

KEYWORDS:

CXCR4; RhoA; colon cancer; microRNA-126 (mir-126)

PMID:
27517626
PMCID:
PMC5312381
DOI:
10.18632/oncotarget.11176
[Indexed for MEDLINE]
Free PMC Article

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