Long noncoding RNA-H19promotes proliferation and Epithelial-Mesenchymal transition through a myc-rel

来源 :中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议 | 被引量 : 0次 | 上传用户:yuan_kai
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  Liver regeneration driven by hepatocyte proliferation is necessary for tissue repair and survival after acute liver injury,liver transplantation,and chronic hepatic disease.After a partial hepatectomy(PHx)in mice,a rapid induction of proliferative factors activates quiescent hepatocytes and primes their subsequent proliferation.During this process,many transcription factors are activated and up-regulate a large number of proliferation-related target genes to repair the liver.c-Myc is a central transcription factor and is essential for total liver regeneration.The up-regulation of c-myc mRNA occurs 30 minutes after PHx and sharply increases after several hours.However,the mechanism of the fast up-regulation of c-myc in early liver regeneration remains elusive.In this study,we reported for the first time that a c-myc-related positive feedback loop contributed to this phenomenon.A long noncoding RNA(lncRNA),H19,stabilized the c-myc mRNA by forming a H19-hnRNP U-myc complex and was transcriptionally up-regulated by c-myc in liver cells.Although many microRNAs,which are a type of noncoding RNA,have been reported to control liver regeneration,H19 is the first lncRNA that is involved in liver regeneration.We also found that H19 promotes an epithelial-to-mesenchymal transition(EMT)in liver cells during regeneration.Conclusion:lncRNA-H19 promotes hepatocyte proliferation and EMT by stabilizing c-myc mRNA in early liver regeneration.Moreover,the existence of a c-myc-related positive feedback loop augmented the effect of c-myc for a short time period during early liver regeneration.
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