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MiR-21 coordinates tumor growth and modulates KRIT1 levels.

ABSTRACT: miR-21 is overexpressed in tumors and it displays oncogenic activity. Here, we show that expression of miR-21 in primary tumors anticorrelates with KRIT1/CCM1, an interacting partner of the Ras-like GTPase Rap1, involved in Cerebral Cavernous Malformations (CCM). We present evidences that miR-21 silences KRIT1 by targeting its mRNA 3'UTR and that this interaction is involved in tumor growth control. In fact, miR-21 over-expression or KRIT1 knock-down promote anchorage independent tumor cell growth compared to controls, whereas the opposite is observed when anti-miR-21 or KRIT1 overexpression are employed. Our findings suggest that miR-21 promotes tumor cell growth, at least in part, by down-modulating the potential tumor suppressor KRIT1.

SUBMITTER: Orso F

PROVIDER: S-EPMC3750217 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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miR-21 coordinates tumor growth and modulates KRIT1 levels.

Orso Francesca F Balzac Fiorella F Marino Marco M Lembo Antonio A Retta Saverio Francesco SF Taverna Daniela D

Biochemical and biophysical research communications 20130718 1

miR-21 is overexpressed in tumors and it displays oncogenic activity. Here, we show that expression of miR-21 in primary tumors anticorrelates with KRIT1/CCM1, an interacting partner of the Ras-like GTPase Rap1, involved in Cerebral Cavernous Malformations (CCM). We present evidences that miR-21 silences KRIT1 by targeting its mRNA 3'UTR and that this interaction is involved in tumor growth control. In fact, miR-21 over-expression or KRIT1 knock-down promote anchorage independent tumor cell grow ...[more]

PMID: 23872064

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Project description:The relationship between miR-21 and miR-182 gene expression in peripheral blood and gastric cancer tissue was investigated, exploring the relationship between the levels of miR-21 and miR-182 and prognosis of gastric cancer patients, and determining the effects of these two genes on the growth and migration of gastric cancer cells. Fifty gastric cancer patients who were treated in the 254th Hospital of PLA, from July 2012 to July 2014 were selected. Peripheral blood samples were drawn from patients, and 50 healthy subjects were studied as controls. The levels of the miR-21 and miR-182 genes were detected by semi-quantitative PCR, and the correlation between miR-21 and miR-182 expression and clinicopathological features was explored. Moreover, the effects of miR-21 and miR-182 expression on the survival time and prognosis of patients were investigated. siRNA was used to downregulate miR-21 and miR-182 gene expression in MGC-803 gastric cancer cells, and MTT and Transwell assays were conducted. As a result, the relative expression levels of miR-21 and miR-182 in peripheral blood of gastric cancer patients were significantly higher than in healthy subjects (p<0.01) and the relative expression of miR-182 was closely related to the clinicopathological features of gastric cancer patients (p<0.05); high expression of miR-21 and miR-182 was associated with reduced survival time of patients (p<0.05); MGC-803 cells with low expression of miR-21 and miR-182 were analyzed, showing that miR-182 promoted cell proliferation and migration (p<0.01). In conclusion, the relative levels of miR-21 and miR-182 in peripheral blood of patients with gastric cancer are significantly increased; low expression of miR-182 can significantly reduce the proliferation and migration of gastric cancer cells. Moreover, miR-182 expression, which is closely related to the clinicopathological features of gastric cancer, can serve as a target for the clinical treatment of gastric cancer.

Dataset Information

MiR-21 coordinates tumor growth and modulates KRIT1 levels.

Publications

miR-21 coordinates tumor growth and modulates KRIT1 levels.

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