MicroRNA Expression Profiling in CCl₄-Induced Liver Fibrosis of Mus musculus.
Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs), small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl₄) and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO) and in-depth pathway enrichment analysis. Herein, we found that four miRNAs were upregulated and four miRNAs were downregulated more than two-fold in CCl₄-treated livers compared to a control liver. Eight miRNAs were predicted to target a total of 4079 genes. GO analysis revealed that those target genes were located in various cellular compartments, including cytoplasm, nucleolus and cell surface, and they were involved in protein-protein or protein-DNA bindings, which influence the signal transductions and gene transcription. Furthermore, pathway enrichment analysis demonstrated that the 72 subspecialized signaling pathways were associated with CCl₄-induced liver fibrosis and were mostly classified into metabolic function-related pathways. These results suggest that CCl₄ induces liver fibrosis by disrupting the metabolic pathways. In conclusion, we presented several miRNAs and their biological processes that might be important in the progression of liver fibrosis; these findings help increase the understanding of liver fibrogenesis and provide novel ideas for further studies of the role of miRNAs in liver fibrosis.
Department of Biological Sciences, Pusan National University, Pusan 46241, Korea. j.hyun@pusan.ac.kr.
Jeongeun
J
Hyun
Department of Microbiology, Pusan National University, Pusan 46241, Korea. jjuwoogi@pusan.ac.kr.
Jungwook
J
Park
Department of Biological Sciences, Pusan National University, Pusan 46241, Korea. s.wang@pusan.ac.kr.
Sihyung
S
Wang
Department of Biological Sciences, Pusan National University, Pusan 46241, Korea. jieun@pusan.ac.kr.
Jieun
J
Kim
Department of Microbiology, Pusan National University, Pusan 46241, Korea. ehyuna92@pusan.ac.kr.
Hyun-Hee
HH
Lee
Department of Microbiology, Pusan National University, Pusan 46241, Korea. yseo2011@pusan.ac.kr.
Young-Su
YS
Seo
Department of Biological Sciences, Pusan National University, Pusan 46241, Korea. y.jung@pusan.ac.kr.
Youngmi
Y
Jung
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D053263:Gene Regulatory Networks; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
D035683:MicroRNAs; D002251:Carbon Tetrachloride
gene ontology; liver fibrosis; microRNA; microarray; mouse