MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluste...MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis.It has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 cluster.Collectively,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 families.Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses.Various targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and metastasis.In this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory loop.In addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.展开更多
Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attrib...Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.展开更多
文摘MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis.It has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 cluster.Collectively,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 families.Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses.Various targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and metastasis.In this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory loop.In addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.
文摘Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.
