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The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas.

ABSTRACT: MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function in gene silencing by post-transcriptional regulation of gene expression. The dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including the development and progression of gliomas. Their small size, stability and ability to target multiple oncogenes have simultaneously distinguished miRNAs as attractive candidates for biomarkers and novel therapeutic targets for glioma patients. In this review, we summarize the most frequently cited miRNAs known to contribute to gliomagenesis and progression by regulating the defining hallmarks of gliomas, including angiogenesis, invasion, and cell metabolism. We also discuss their promising potential as prognostic and predictive biomarkers and novel therapeutic targets, in addition to the challenges that must be overcome before their translation from bench to bedside.

SUBMITTER: Beyer S

PROVIDER: S-EPMC5532621 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas.

Beyer Sasha S Fleming Jessica J Meng Wei W Singh Rajbir R Haque S Jaharul SJ Chakravarti Arnab A

Cancers 20170710 7

MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function in gene silencing by post-transcriptional regulation of gene expression. The dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including the development and progression of gliomas. Their small size, stability and ability to target multiple oncogenes have simultaneously distinguished miRNAs as attractive candidates for biomarkers and novel therapeutic targets for glioma patients. In this review, we ...[more]

PMID: 28698530

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Project description:Although devascularization caused by antiangiogenic therapy limits tumor growth, the benefits of antiangiogenic therapy are often transient, with tumor growth typically resuming through adaptive responses that need further characterization. Recent reports indicate that hypoxia in tumor microenvironments induces autophagy, a lysosomal degradation pathway that may promote tumor cell survival. We investigated the hypothesis that antiangiogenic therapy leads to hypoxia, which induces tumor cell autophagy as a cytoprotective adaptive response promoting evasion to antiangiogenic therapy. We found that patient specimens from glioblastomas evasive to bevacizumab exhibited nearly 80% more hypoxia than did pretreatment specimens from the same patients. Hypoxia (1% oxygen) induced autophagy in several primary glioblastoma cells and cell lines. Selective autophagy occurred independent of HIF-1?/AMPK hypoxia-upregulated pathways, while nonselective autophagy depended on both. Autophagy inhibitors transitioned hypoxic glioblastoma cells from autophagy to nonapoptotic cell death. Patient specimens from glioblastomas evading antiangiogenic therapy expressed 55% more autophagy-related BNIP3 than did pretreatment specimens from the same patients, with BNIP3 expression localizing to the increased hypoxic areas seen in the glioblastomas that evaded antiangiogenic therapy. Human glioblastoma xenografts exhibited persistent growth inhibition when treated with autophagy inhibitor chloroquine plus antiangiogenic bevacizumab; chloroquine prevented the evasive hypoxia-associated growth seen with bevacizumab alone and reversed the more than 2-fold increased expression of autophagy mediator BNIP3 seen in xenografts growing during bevacizumab monotherapy. These findings suggest that hypoxia-mediated autophagy promotes tumor cell survival after antiangiogenic therapy, a novel adaptive response to antiangiogenic therapy that can be pharmacologically disrupted to allow antiangiogenic therapy to fulfill its therapeutic promise.

Dataset Information

The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas.

Publications

The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas.

Similar Datasets

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