Identification of MicroRNAs Involved in Growth Arrest and Apoptosis in Hydrogen Peroxide-Treated Human Hepatocellular Carcinoma Cell Line HepG2.
Although both oxidative stress and microRNAs (miRNAs) play vital roles in physiological and pathological processes, little is known about the interactions between them. In this study, we first described the regulation of H2O2 in cell viability, proliferation, cycle, and apoptosis of human hepatocellular carcinoma cell line HepG2. Then, miRNAs expression was profiled after H2O2 treatment. The results showed that high concentration of H2O2 (600 μM) could decrease cell viability, inhibit cell proliferation, induce cell cycle arrest, and finally promote cell apoptosis. Conversely, no significant effects could be found under treatment with low concentration (30 μM). miRNAs array analysis identified 131 differentially expressed miRNAs (125 were upregulated and 6 were downregulated) and predicted 13504 putative target genes of the deregulated miRNAs. Gene ontology (GO) analysis revealed that the putative target genes were associated with H2O2-induced cell growth arrest and apoptosis. The subsequent bioinformatics analysis indicated that H2O2-response pathways, including MAPK signaling pathway, apoptosis, and pathways in cancer and cell cycle, were significantly affected. Overall, these results provided comprehensive information on the biological function of H2O2 treatment in HepG2 cells. The identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for liver cancer.
Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, China; Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.
Yuan
0000-0001-8081-7237
Y
Luo
Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.
Xinyu
X
Wen
Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.
Ling
L
Wang
Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.
Jing
J
Gao
Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, China.
Zi
Z
Wang
Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, China.
Chunyan
C
Zhang
Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, China.
Pengjun
P
Zhang
Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.
Chengrong
C
Lu
Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.
Lianning
0000-0003-1187-8655
L
Duan
Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, China; Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.
Yaping
0000-0001-9169-5095
Y
Tian
D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D060066:Protein Interaction Maps; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide