• Regulation of aerobic glycolysis by microRNAs in gastric cancer
  • Elham kamalkazemi,1 Masoumeh Amani,2 Effat alizadeh,3,*
    1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
    2. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    3. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran


  • Introduction: One major hallmark of gastric cancer (GC) cells is rapid growth and uncontrolled proliferation, which requires high energy. Consequently, GC cells must alter their metabolic process from oxidative phosphorylation to aerobic glycolysis to satisfy the energy, needed for rapid proliferation (1). This phenomenon of changes in tumor cellular metabolism is known as “metabolic reprogramming”, mediated by higher glucose uptake, enhanced expression of glycolysis-related enzymes such as HK-II, PKM2, and conversion of pyruvate to lactic acid (2). Emerging evidence reports that miRNAs, as a class of non-coding RNAs can target and bind to the 3′-untranslated region (UTR) located on mRNA of enzymes involved in metabolic processes and glucose transporters and inhibit their expression. Therefore, microRNAs can act as important regulators of metabolic reprogramming in GC cells and suppress their growth, invasion, and metastasis (3). Based on these characteristics, in the present study, we reviewed the role of some miRNAs in regulation of GC cell's metabolic reprogramming.
  • Methods: In the present study, we did a comprehensive literature review of the results of related articles published between 2022 and 2023 from PubMed and Google Scholar databases with keywords such as “gastric cancer”, “glycolysis”, “metabolic reprogramming” AND “microRNA” queries.
  • Results: In the present study, we summarized some microRNAs' role in regulating the glycolytic metabolism of GC. We observed that these microRNAs can directly or indirectly target the expression of glycolytic genes. For example, MicroRNA-181b (4), MiR‐5683 (5), miR‑449c (6), MiR-let-7a (7), and miR‐148b (8) downregulate the expression hexokinase II, pyruvate dehydrogenase kinase 4, PFKFB3, PKM2 and SLC2A1 in GC, respectively. Subsequently, downregulation of these glycolytic metabolism-related enzyme expressions, can reduce glucose uptake and consumption, lactate production, and cellular ATP levels and lead to proliferation and growth suppression in GC cells. Therefore, miRNAs have a key duty as important regulators of glucose metabolism.
  • Conclusion: Understanding the function of microRNAs in reprogramming the glycolytic metabolism pathway in GC provides novel insights into the potential therapeutic strategies in GC patients.
  • Keywords: MicroRNAs, Metabolic reprogramming, Glycolysis, Gastric cancer