ABSTRACT
It is well accepted that HBx plays the major role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. However, little was known about its role in regulating long noncoding RNAs (lncRNAs), a large group of transcripts regulating a variety of biological processes including carcinogenesis in mammalian cells. Here we report that HBx upregulates UCA1 genes and downregulates p27 genes in hepatic LO2 cells. Further studies show that the upregulated UCA1 promotes cell growth by facilitating G1/S transition through CDK2 in both hepatic and hepatoma cells. Knock down of UCA1 in HBx-expressing hepatic and hepatoma cells resulted in markedly increased apoptotic cells by elevating the cleaved caspase-3 and caspase-8. More importantly, UCA1 is found to be physically associated with enhancer of zeste homolog 2 (EZH2), which suppresses p27Kip1 through histone methylation (H3K27me3) on p27Kip1 promoter. We also show that knockdown of UCA1 in hepatoma cells inhibits tumorigenesis in nude mice. In a clinic study, UCA1 is found to be frequently up-regulated in HBx positive group tissues in comparison with the HBx negative group, and exhibits an inverse correlation between UCA1 and p27Kip1 levels. Our findings demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-UCA1/EZH2-p27Kip1 axis, and a potential target of HCC.
Subject(s)
Carcinogenesis/genetics , Cell Transformation, Viral/genetics , Enhancer of Zeste Homolog 2 Protein/genetics , Liver Neoplasms/genetics , RNA, Long Noncoding/genetics , Trans-Activators/genetics , Animals , Cell Proliferation , Cyclin-Dependent Kinase 2/genetics , Cyclin-Dependent Kinase Inhibitor p27/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/virology , Membrane Proteins , Mice , Mice, Nude , Neoplasm Transplantation , Serine Endopeptidases , Signal Transduction , Transfection , Viral Regulatory and Accessory ProteinsABSTRACT
Through sampling investigation of fouling organisms on the enhancement artificial reefs set up in Laizhou Bay, it was proved that oyster (Ostrea plicatula) was the dominant fouling species. Therefore the dry mass of shell (Ms), total fresh mass (Mt) and thickness (T) of oyster attached on the reefs were analyzed. The results showed that the Mt and Ms presented seasonal variation (P < 0.01), that is, the values were the lowest in April and the highest in December. The reef age and the length of the time the enhancement reefs placed in the sea had significant effect on Mt, Ms and T. With the increment of reef ages, all indices increased obviously. The carbon sinks of oysters attaching to the tube enhancement reefs constructed in 2009, 2010 and 2011 in Laizhou Bay were 17.61, 16.33 and 10.45 kg · m(-3), respectively. The oysters on the enhancement reefs of Jincheng marine ranch with an area of 64.25 hm2 had fixed carbon of 297.5 t C (equivalent to 1071 t of CO2) from 2009 to 2013 in Laizhou Bay. To capture and store the same amount of CO2 would cost about 1.6 x 10(5)-6.4 x 10(5) US dollars. Therefore, oysters attaching to the enhancement reefs bring about remarkable ecological benefits.