Evolution of hepatitis B virus and its promotion effect on hepatocellular carcinoma / 中国热带医学

@#Abstract: Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC) in China. The occurrence of HCC through chronic inflammation follows the Darwinian evolutionary law, known as "mutation-selection-adaptation". Inflammatory mutagenic molecules promote the generation of somatic mutations, and the most mutant cells are eliminated by inflammatory microenvironment. However, a minority of mutant cells survive the selective pressure and develop to tumor initial cells by activating oncogenic signaling pathway and acquiring "stemness" characteristics. Alongside this process, HBV also evolves under the pressure of inflammatory microenvironment, which is characterized by the accumulation of cancer-promoting viral mutations, reducing the ability to infect new individuals. The high-risk mutant strains are eliminated with the death of hosts, leading to a phenomenon termed as "dead-end evolution". HBV evolution contributes to cancer evolution by maintaining the inflammatory microenvironment, activating oncogenic pathways, inducing somatic cell mutations, and altering metabolic patterns. The combo mutations of HBV and HBV integrations can be applied to predict the occurrence and prognosis of HCC. Anti-viral treatment reduces the risk of HCC by relieving inflammation. This article reviews the molecular epidemiological evidence and mechanistic advances related to the co-evolution of HBV and HCC. Clarifying the co-evolutionary pattern of virus and cancer and the key molecular events involved, is beneficial for identifying new biomarkers and therapeutic targets, thus improving the prevention and treatment strategies for HCC.

The deubiquitinase USP38 affects cellular functions through interacting with LSD1

BACKGROUND: Deubiquitination is a posttranslational protein modification prevalent in mammalian cells. Deubiquitinases regulate the functions of the target protein by removing its ubiquitin chain. In this study, the effects of the deubiquitinase USP38's functions on the LSD1 protein and on cell physiology were investigated. MATERIALS AND METHODS: Western blotting, real-time quantitative PCR, immunoprecipitation, denaturing immunoprecipitation and luciferase reporter assays were used to analyze the protein stability, protein interactions and changes in the ubiquitin chain. Cell proliferation assays, colony formation assays, drug treatments and western blotting were used to explore the functions of USP38 in cells. RESULTS: The deubiquitinase USP38 stabilizes protein LSD1 in cells by binding LSD1 and cleaving its ubiquitin chain to prevent the degradation of LSD1 by the intracellular proteasome. USP38 enhances the ability of LSD1 to activate signaling pathways and hence promotes cellular abilities of proliferation and colony formation through interacting with LSD1. Furthermore, USP38 enhances the drug tolerance of human colon cancer cells. CONCLUSIONS: USP38 is an LSD1-specific deubiquitinase that affects cellular physiology through interacting with LSD1.

Mycoplasma hyorhinis and Mycoplasma fermentans induce cell apoptosis and changes in gene expression profiles of 32D cells

Infection of mycoplasmas has been linked to various human diseases including arthritis, pneumonia, infertility and cancer. While Mycoplasma hyorhinis and Mycoplasma fermentans have been detected in gastric adenocarcinomas, the mechanisms underlyine the pathogenesis are unknown. In this study, cell growth kinetics, Hoechst 33258 staining, DNA ladder assays, Western blotting analysis and cDNA microarray assays were performed to investigate the roles of M. hyorhinis and M. fermentans during infection of mammalian cells. Our data demonstrated that these mycoplasmas inhibid the growth of immortalised cell lines (32D and COS-7) ane tumor cell lines (HeLa and AGS). In addition, the infection of the 32D cell line with M. hyorhinis and M. fermentans induced compression of the nucleus, degradation of the cell genome and dysregulation of the expression of genes related to proliferation, apoptosis, tumorigenesis, signaling pathway and metabolism. Apoptosis related proteins Bcl-2, Bid and p53 were down-regulated, Fas was up-regulated and Bax was dysregulated in mycoplasma-infected 32D cells. Together, our data demonstrated that infection of mycoplasmas inhibitd cele growts through modification of gene expression profiles and post-translation modification of proliferation and apoptosis related proteins.