It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Chronic hepatitis B virus infection is a major risk factor for hepatocellular carcinoma. HBV infection affects lncRNA expression in infected cells, but the detailed mechanism and biological significance are not yet clear. In this study, we focused on exploring the function of the HBV-upregulated lncRNA SAMD12-AS1 in cell proliferation. We found that there is a higher level of SAMD12-AS1 expression in tumors than in adjacent nontumorous liver tissues. We showed that ectopic expression of SAMD12-AS1 promotes cell growth and blocks apoptosis, while knockdown of SAMD12-AS1 inhibits cell proliferation and enhances etoposide-induced apoptosis. Using RNA immunoprecipitation and mass spectrometry, we determined that SAMD12-AS1 interacts with NPM1 and confirmed that SAMD12-AS1(1-350) is required for the interaction with NPM1. As it is known that NPM1 interacts with the E3 ligase HDM2 and reduces HDM2-mediated p53 degradation, we examined whether SAMD12-AS1 can affect p53 stability. Overexpression of SAMD12-AS1 caused a reduction in p53 protein levels by shortening its half-life. Conversely, knockdown of SAMD12-AS1 prolonged the half-life of p53. We further demonstrated that SAMD12-AS1 increased the interaction of HDM2 and p53 and enhanced p53 ubiquitination. Our findings reveal that HBV-upregulated SAMD12-AS1 regulates cell proliferation and apoptosis via the NPM1-HDM2-p53 axis.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming, China
2 Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China
3 Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; University of Chinese Academy of Sciences, Beijing, China
4 302 Hospital of PLA, Beijing, China
5 Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China