A new study has determined the role of a microRNA in suppressing the Warburg effect in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. The Warburg effect is one of the major metabolic changes of cancer cells, which is characterized by high rates of glucose uptake and lactate production even in the presence of oxygen, leading to a state termed aerobic glycolysis. Most cancer cells, including HCC cells, display this fundamental change in their cellular metabolism to meet the increased energetic and anabolic demands required for rapid cell growth.
Research done by Dr. Yunfei Yuan and team at the Sun Yat-sen University Cancer Centre in China demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in HCC. MiR-199a-5p directly targets the 3′-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells. Moreover, under hypoxic conditions, the expression of miR-199a-5p is suppressed by the up-regulation of HIF-1α. Thus, mutual regulation between miR-199a-5p and HIF-1α forms a positive feedback loop to promote glycolysis in HCC cells.
The data from this study define a new mechanism contributing to the Warburg effect and also indicate miR-199a-5p as a potential therapeutic target for HCC.