title: Functional study of miR-27a in human hepatic stellate cells by proteomic analysis: comprehensive view and a role in myogenic tans-differentiation.
abstract: We previous reported that miR-27a regulates lipid metabolism and cell proliferation during hepatic stellate cells (HSCs) activation. To further explore the biological function and underlying mechanisms of miR-27a in HSCs, global protein expression affected by overexpression of miR-27a in HSCs was analyzed by a cleavable isotope-coded affinity tags (cICAT) based comparative proteomic approach. In the present study, 1267 non-redundant proteins were identified with unique accession numbers (score ≥1.3, i.e. confidence ≥95%), among which 1171 were quantified and 149 proteins (12.72%) were differentially expressed with a differential expression ratio of 1.5. We found that up-regulated proteins by miR-27a mainly participate in cell proliferation and myogenesis, while down-regulated proteins were the key enzymes involved in de novo lipid synthesis. The expression of a group of six miR-27a regulated proteins was validated and the function of one miR-27a regulated protein was further validated. The results not only delineated the underlying mechanism of miR-27a in modulating fat metabolism and cell proliferation, but also revealed a novel role of miR-27a in promoting myogenic tans-differentiation during HSCs activation. This study also exemplified proteomics strategy as a powerful tool for the functional study of miRNA.
authors.affiliation: Key Laboratory of Neuroregeneration, Nantong University, Nanton, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Medical School of Nantong University, Nantong, PR China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, Medical School of Nantong University, Nantong, PR China.
authors.forename: Juling
authors.initials: J
authors.lastname: Ji
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D054338:Cell Transdifferentiation / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D060588:LIM Domain Proteins / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D009124:Muscle Proteins; D034741:RNA, Small Interfering