Sensitization of hepatocellular carcinoma cells to irradiation by miR‑34a through targeting lactate dehydrogenase‑A.

Abstract

Radiation is a therapeutic strategy for the treatment of cancer, and is also used for the treatment of hepatocellular carcinoma. MicroRNAs (miRs) are endogenous, non‑coding single‑stranded RNA molecules, which regulate gene expression at the post‑transcriptional level. In the present study, the roles of miR‑34a‑mediated glycolysis in radiation sensitivity were investigated. By establishing a radioresistant liver cancer cell line, the present study compared the expression level of miR‑34a from radiosensitive and radioresistant cells using the reverse transcription‑quantitative polymerase chain reaction. The glucose uptake and lactate production were also compared between the two types of cells. The results demonstrated that miR‑34a acted as a tumor suppressor in human hepatocellular cancer cells. Following comparison of radiosensitive and radioresistant cancer cells, the results of the present study demonstrated that miR‑34a was negatively correlated with radiation resistance; and levels of miR‑34a were significantly downregulated in the HepG2 radioresistant cells. Furthermore, the rate of glycolysis in the radioresistant cells was elevated, and there was evidence that glucose uptake and lactate production increased. Lactate dehydrogenase A (LDHA), which is a key enzyme in the glycolysis signaling pathway, was found to be a target of miR‑34a in hepatocellular cancer cells. Notably, the overexpression of miR‑34a re‑sensitized HepG2 radioresistant cells to radiation treatment by inhibiting LDHA. The results of the present study revealed a negative correlation between miR‑34a and glycolysis, caused by the targeting of LDHA‑34a, providing a novel mechanism for miR‑34a‑mediated radioresistance.