[Research progress of mouse model of hepatitis B virus infection].

Hepatitis B virus (HBV) infection is a global health problem. Animal models are important for the study of the HBV infection mechanism. In the study related to the mouse model of HBV infection, the researchers have established a variety of mouse models, including transgenic, plasmid hydrodynamic injection, virus vector transfection, cccDNA cycle simulation, human and mouse liver chimerism, and liver/immune dual humanization, according to the characteristics of HBV infection. Herein, the research progress of these models is summarized. Notably, the application of these models can further clarify the mechanism of HBV infection under the conditions of a specific immune response in vivo and lay the foundation for the development of new antiviral drugs and immunotherapy for HBV infection.

Analyzing the association between XRCC1 c.1804C>A genetic variant and lung cancer susceptibility in the Chinese population.

Lung cancer is the most common cancer occurring worldwide. The human X-ray repair complementing group 1 (XRCC1) gene is one of the most important candidate genes that influence the susceptibility to lung cancer. The objective of this study was to analyze the potential association between the c.1804C>A genetic variant of XRCC1 and lung cancer susceptibility. A total of 703 subjects were recruited for this study. Genotyping of c.1804C>A genetic variant was performed using the created restriction site-polymerase chain reaction. Statistically significant differences in allele frequencies and genotype were found between lung cancer patients and cancer-free controls. The genotype AA was statistically associated with the increased risk of lung cancer when compared to the wild genotype, CC, and the carrier genotype, CA/CC (AA vs CC: OR = 2.71, 95%CI = 1.57-4.67, P < 0.001; AA vs CA/CC: OR = 2.54, 95%CI = 1.50-4.29, P < 0.001). The allele A likely contributes to the susceptibility to lung cancer (A vs C: OR = 1.47, 95%CI = 1.17-1.84, P = 0.001). Our data indicates that the c.1804C>A genetic variant of XRCC1 is statistically associated with the susceptibility to lung cancer in the Chinese population.

Trans-activation of heparanase promoter by ETS transcription factors.

The remodeling of extracellular matrix (ECM) is an important process required for cancer cells to turn into invasive and metastatic cancer cells. To dissolve the protein components of ECM, matrix metalloproteinases are some of the essential enzymes. Another ECM remodeling enzyme is the heparanase (Hpa) that digests the heparin sulfate component of the matrix. In metastatic cancer cells the Hpa gene is upregulated. To investigate the mechanism of why Hpa was upregulated in metastatic cancer cells, the regulatory sequence of heparanase gene was isolated and its function analysed in metastatic breast cancer cells. We found there are four ETS transcription factor binding sites. Two of them flanking the transcription initiation of the Hpa gene are nonfunctional, whereas two others are highly functional and responded to exogenously added ETS transcription factors. Mutation of these two ETS binding sites abolished the transcriptional activation of Hpa promoter by ETS transcription factors. Among four transcription factors tested (ETS1, ETS2, PEA3, and ER81), ETS1 and ETS2 are more potent in transactivating the human Hpa gene. Furthermore, dominant-negative ETS transcription factors failed to transactivate Hpa promoter and could abrogate the function of wild-type transcription factor in transactivation activity of ETS transcription factors on the Hpa promoter. These results suggest that ETS transcription factors play an important role in tumor invasion and metastasis by modulating the remodeling of ECM.