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MiR-130a Deregulates PTEN and Stimulates Tumor Growth.

ABSTRACT: H-RasV12 oncogene has been shown to promote autophagic cell death. Here, we provide evidence of a contextual role for H-RasV12 in cell death that is varied by its effects on miR-130a. In E1A-immortalized murine embryo fibroblasts, acute expression of H-RasV12 promoted apoptosis, but not autophagic cell death. miRNA screens in this system showed that miR-130a was strongly downregulated by H-RasV12 in this model system. Enforced expression of miR-130a increased cell proliferation in part via repression of PTEN. Consistent with this effect, miR-130a overexpression in human breast cancer cells promoted Akt phosphorylation, cell survival, and tumor growth. In clinical specimens of multiple human cancers, expression of miR-130 family members correlated inversely with PTEN expression. Overall, our results defined miR-130a as an oncogenic miRNA that targets PTEN to drive malignant cell survival and tumor growth. Cancer Res; 77(22); 6168-78. ©2017 AACR.

SUBMITTER: Wei H

PROVIDER: S-EPMC7081380 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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miR-130a Deregulates PTEN and Stimulates Tumor Growth.

Wei Huijun H Cui Ri R Bahr Julian J Zanesi Nicola N Luo Zhenghua Z Meng Wei W Liang Guang G Croce Carlo M CM

Cancer research 20170921 22

H-RasV12 oncogene has been shown to promote autophagic cell death. Here, we provide evidence of a contextual role for H-RasV12 in cell death that is varied by its effects on miR-130a. In E1A-immortalized murine embryo fibroblasts, acute expression of H-RasV12 promoted apoptosis, but not autophagic cell death. miRNA screens in this system showed that miR-130a was strongly downregulated by H-RasV12 in this model system. Enforced expression of miR-130a increased cell proliferation in part via repre ...[more]

PMID: 28935812

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