title: miR-181b promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients.
abstract: MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because of the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-β1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-β1 pathway by a currently unknown mechanism.
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Baocan
authors.initials: B
authors.lastname: Wang
authors.forename: Wenxi
authors.initials: W
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiangao
authors.initials: J
authors.lastname: Fan
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D050760:Cyclin-Dependent Kinase Inhibitor p27