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MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities

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Review

MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities

Abraham Pedroza-Torres et al. Front Oncol.

Abstract

Dysregulated metabolism is a common feature of cancer cells and is considered a hallmark of cancer. Altered tumor-metabolism confers an adaptive advantage to cancer cells to fulfill the high energetic requirements for the maintenance of high proliferation rates, similarly, reprogramming metabolism confers the ability to grow at low oxygen concentrations and to use alternative carbon sources. These phenomena result from the dysregulated expression of diverse genes, including those encoding microRNAs (miRNAs) which are involved in several metabolic and tumorigenic pathways through its post-transcriptional-regulatory activity. Further, the identification of key actionable altered miRNA has allowed to propose novel targeted therapies to modulated tumor-metabolism. In this review, we discussed the different roles of miRNAs in cancer cell metabolism and novel miRNA-based strategies designed to target the metabolic machinery in human cancer.

Keywords: microRNAs; regulation; reprogramming metabolism; therapeutic targets; tumor cell metabolism.

Figures

Figure 1
Figure 1
Drugs with clinical potential in cancer that modulate miRNAs implicated in cell metabolism. In boxes are shown drugs that potentially modulate the main miRNAs involved in the metabolic reprogramming of tumor cells. Increased glycolysis flow, alteration of the PI3K/AKT/mTOR pathway, and epithelial-mesenchymal transition (EMT) are key processes that allow tumor cells to reprogram their metabolism in order to survive, proliferate, migrate, and evade new niches. Different miRNAs participate in these processes inhibiting the expression of enzymes (e.g., HK2, PKM2, IRS1, PI3K, AKT, mTOR), transcription factors (e.g., SP1, SIX1, ZEB1, ZEB2, GABPA), and cellular receptors (e.g., GLUT3, ESRRG).
Figure 2
Figure 2
Pharmacological-targeting of tumor metabolism and miRNA-modulating networks of drugs tested in clinical trials or already approved FDA drugs for cancer treatments. It is reported that dysregulations of miRNAs contribute to therapy resistance via drug efflux mechanisms, alterations in drug targets, energy metabolism, Glutamine metabolism, lactate metabolism, cholesterol metabolism, among others.
Figure 3
Figure 3
Life style and diet has an impact on different metabolic mechanisms in human cells. Disruption of metabolic fluxes, might particularly affect expression of genes and miRNAs related to control of cell proliferation, cell cycle, and adhesion, eventually leading or favoring neoplastic processes to take place in different organs (i.e., Breast, Prostate, Lung, Colon, etc.). Microbiota, on the other side, the new star player in the complex interaction between environment and human organism, can also influence the effect of nutrients or drug intake within host. In an unhealthy weight scenario (i.e., obesity), disequilibrium in adipogenesis leads to chronic inflammation and triggering of signals for over-expression of oncomiRs. Under this condition, dysbiosis (e.g., loss of balance in gut bacteria composition) could further concur to sustain or even enhance the metabolic perturbations favoring neoplastic transformations.

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