title: 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.
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Niu
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Luo
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D005720:Gamma Rays; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D007770:L-Lactate Dehydrogenase