Abstract P4-07-05: MicroRNA-27b mediates deregulation of energy metabolism in breast cancer

Abstract

Abstract MicroRNAs (miRNAs) are a class of small, non-coding RNA which participate in gene regulation by targeted silencing of specific mRNA transcripts. Recently, it has become clear that dysfunctional miRNA expression is an important contributor to the deregulation of key signaling pathways underlying carcinogenesis. MicroRNA-27b is an example of one such pro-oncogenic miRNA, and correspondingly, its expression has been found to be upregulated in breast cancer cells and tissues. In this regard, several targets of miR-27b have previously been verified, and implicate miR-27b in multiple neoplastic processes including migration, invasion and metastasis. In order to enable future development of miRNA-based cancer therapies, the putative targets of each miRNA must be mapped more comprehensively. Such awareness is necessary in order to make informed choices regarding whether a miRNA-based therapy is likely to be effective and what side-effects should be anticipated. Therefore, this project seeks to further establish the role of miR-27b in the context of breast cancer, specifically by identifying novel target transcripts under its control. Using target prediction algorithms and breast cancer cell culture models, initial evidence has implicated Pyruvate Dehydrogenase Protein X (PDHX) to be a probable target. As a structural component of the Pyruvate Dehydrogenase Complex, the role of PDHX in linking the end products of glycolytic reactions with subsequent oxidative phosphorylation pathways is indispensable. However, a hallmark of cancer cell metabolism is the propensity to consume glucose aerobically, which liberates additional carbon skeletons for use in biosynthetic reactions that are crucial for tumor growth. In this way, miR-27b overexpression appears to sever the link between glycolysis and subsequent catabolic pathways, thus conferring a pro-growth advantage to the cancer cells. Expression profiling of PDHX using both breast cancer cell lines and human breast tissues (which overexpress miR-27b) reveal that PDHX levels are indeed significantly reduced, thus supporting the notion that miR-27b alters cancer cell metabolism specifically by targeting this gene in breast cancer. Improving the current understanding of miR-27b's functions will lay the necessary ground work to evaluate its potential as a novel target for cancer therapy. Similarly, the awareness of the expression status of miR-27b and its targets in breast cancer tumors will further efforts to find suitable miRNA tissue biomarkers to enhance screening and prognosis. In this way, microRNA-based approaches offer the distinct potential to improve cancer detection as well as treatment, making them a dynamic method to improve management of breast cancer patients in the future. Citation Format: Eastlack SC, Alahari SK, Dong S, Cole JT. MicroRNA-27b mediates deregulation of energy metabolism in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-05.