Suppression of PDHX by microRNA-27b deregulates cell metabolism and promotes growth in breast cancer

Molecular Cancer
Steven C EastlackSuresh K Alahari

Abstract

The disruption of normal gene regulation due to microRNA dysfunction is a common event in cancer pathogenesis. MicroRNA-27b is an example of an oncogenic miRNA, and it is frequently upregulated in breast cancer. MicroRNAs have been found to deregulate tumor metabolism, which typically manifests as heightened cellular glucose uptake in consort with increased flux through glycolysis, followed by the preferential conversion of glycolytic pyruvate into lactate (a phenomenon known as the Warburg Effect). Pyruvate Dehydrogenase, an enzyme complex linking glycolysis with downstream oxidative metabolism, represents a key location where regulation of metabolism occurs; PDHX is a key structural component of this complex and is essential for its function. We sought to characterize the role of miR-27b in breast cancer by identifying novel transcripts under its control. We began by utilizing luciferase, RNA, and protein assays to establish PDHX as a novel target of miR-27b. We then tested whether miR-27b could alter metabolism using several metabolite assay kits and performed a seahorse analysis. We also examined how the altered metabolism might affect cell proliferation. Lastly, we confirmed the relevance of our findings in human breast tu...Continue Reading

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Methods Mentioned

BETA
antisense oligomer
transfection
Assay
PCR
protein assay
electrophoresis
miRNA-Seq
RNA-seq

Software Mentioned

RNAhybrid
PITA
GraphPad Prism
R
miRWalk
Seahorse XF - 24
Genomic Data Commons
RNA22
TargetScan
miRanda

Related Concepts