Abstract: Objective To investigate the effect of TSA on the expression of microRNA-34 family (miR-34a/b/c) and to explore the molecular mechanism of TSA for inhibiting glycolysis in human hepatocellular carcinoma (HCC) cells. Methods Real-time PCR analysis was conducted to evaluated the expression levels of miR-34 family in HCC cells with TSA treatment. The expression of specific genes involved in the regulation of glycolysis was determined by using Real-time PCR in HCC cells with miR-34b overexpression or TSA treatment. The effect of miR-34b or TSA treatment on the glycolysis in HCC cells was investigated by detecting the cellular lactate production and glucose consumption. Rescue assay was performed to clarify the correlation between TSA, miR-34b, and the regulation of glycolysis in HepG2 cells. Results The expression of miR-34b is increased in HepG2 and PLC/PRF/5 HCC cells with TSA treatment (P<0.01). Enforced expression of miR-34b leads to reduced levels of LDH-A in these two cells (P<0.05). Rescue assay reveals that inhibition of miR-34b to prevent the TSA induction results in suppressed glycolysis in HepG2 HCC cells. Conclusion TSA inhibits the metabolic shift in HCC cells via inducing the expression of miR-34b.

Key words: Epigenetic drugs, miR-34, HCC, Warburg effect