MicroRNAs as Regulators of Cancer Cell Energy Metabolism

Abstract

To adapt to the tumor environment or to escape chemotherapy, cancer cells rapidly reprogram their metabolism. The hallmark biochemical phenotype of cancer cells is the shift in metabolic reprogramming towards aerobic glycolysis. It was thought that this metabolic shift to glycolysis alone was sufficient for cancer cells to meet their heightened energy and metabolic demands for proliferation and survival. Recent studies, however, show that cancer cells rely on glutamine, lipid, and mitochondrial metabolism for energy. Oncogenes and scavenging pathways control many of these metabolic changes, and several metabolic and tumorigenic pathways are post-transcriptionally regulated by microRNA (miRNAs). Genes that are directly or indirectly responsible for energy production in cells are either negatively or positively regulated by miRNAs. Therefore, some miRNAs play an oncogenic role by regulating the metabolic shift that occurs in cancer cells. Additionally, miRNAs can regulate mitochondrial calcium stores and energy metabolism, thus promoting cancer cell survival, cell growth, and metastasis. In the electron transport chain (ETC), miRNAs enhance the activity of apoptosis-inducing factor (AIF) and cytochrome c, and these apoptosome proteins are directed towards the ETC rather than to the apoptotic pathway. This review will highlight how miRNAs regulate the enzymes, signaling pathways, and transcription factors of cancer cell metabolism and mitochondrial calcium import/export pathways. The review will also focus on the metabolic reprogramming of cancer cells to promote survival, proliferation, growth, and metastasis with an emphasis on the therapeutic potential of miRNAs for cancer treatment.

Sex-Specific miRNA Differences in Liquid Biopsies from Subjects with Solid Tumors and Healthy Controls

“…Further important epigenetic gene regulators are a special class of small non-coding RNAs, the miRNAs. Through their dynamic interaction with messenger RNA (mRNA), they are involved in post-translational regulation and play an important role in various biological processes, such as regulating energy metabolism, cell senescence, and apoptosis [ 9 , 10 , 11 ]. For instance, miR-92a has been shown not only to induce cell proliferation in cancer cells but it is involved in apoptosis as well [ 12 , 13 ].…”

“…In order to meet their increased energy demands during growth, the glucose metabolism of cancer cells is often accelerated through higher levels of glucose transporters (GLUT). MiR-195, miR-186, and miR-22 directly target the 3′UTRs of several GLUT s and are, therefore, involved in cancer cell energy metabolism [ 10 ].…”

Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response

“…It should be noted that fatty acids may also directly contribute to cell proliferation and regulation of cell metabolism. In stark contrast to normal cells, cancer cells exhibit an insatiable demand for energy, membrane constituents, and regulatory factors to facilitate their rapid proliferation (73)(74)(75). Consequently, extensive metabolic reprogramming becomes imperative to sustain this aberrant growth.…”

Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism

“…Significantly, PRPS1 and RPIA, which are simultaneously elevated in CRC samples, might serve as potential markers for the poorly unknown CRC prognosis. Numerous investigations have shown that 6-Phosphogluconate dehydrogenase (6PGD) is upregulated in many malignancies ( 140 ). 6PGD has been identified as a functioning target of miR-206 and miR-613 in lung tumor cells, and miR-206 and miR-613 are thought to influence 6PGD expression and metabolic switching in cisplatin-resistant ovarian and lung tumor cells ( 141 , 142 ).…”

“…The regulation of PGC-1 by miR-23a may potentially assist the metabolic shift from OXPHOS to anaerobic glycolysis to produce anabolic precursors and support tumor cell growth ( 153 ). Until recently, the importance of the TCA cycle and the control of its activity was underestimated ( 140 ). Pyruvate dehydrogenase protein X component (PDHX) was shown to be a primary target of miR-26a in CRC cells, reported Chen and collaborators ( 154 ), and it is known that miR-26a may modify PDHX expression through specifically targeting the 3′UTR of PDHX.…”