ABSTRACT
Mitochondria are essential for hepatitis B virus (HBV) infection. Moreover, the findings of our previous study indicate that host mitochondrial genetic factors are associated with chronic hepatitis B (CHB) for the Han Chinese. However, in terms of genetic heterogeneity, the impact of mitochondria on host susceptibility to HBV infection in ethnic minorities in China remains unclear. Here, a total of 7070 subjects who had visited the hospital between June 1, 2019, and April 31, 2020, were enrolled for seroprevalence of HBV infection investigation. A total of 220 individuals with CHB (CHBs) and 223 individuals with a trace of HBV infection (spontaneously recovered subjects, SRs) were analyzed for mitochondrial DNA (mtDNA) sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between CHBs and SRs. Among eight nationalities, Yi nationality patients had the highest HBsAg prevalence rate (27.9% [95% CI: 25.3%-30.5%]) and the lowest vaccination rate (4.9% [95% CI: 3.7%-6.2%]). After adjustment for age and gender, haplogroup F was a risk factor for CHB infection (P = 0.049, OR = 2.079, 95% CI = 1.002-4.31), while D4 had a significant negative correlation with the HBeAg-positive rate (P = 0.024, OR = 0.215, 95% CI = 0.057-0.816). Together with our previous study, the findings indicate that different nationalities have different genetic susceptibility to HBV infection.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , China/epidemiology , DNA, Mitochondrial/genetics , DNA, Viral , Ethnicity/genetics , Genetic Predisposition to Disease , Hepatitis B/epidemiology , Hepatitis B/genetics , Hepatitis B Surface Antigens/genetics , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/genetics , Humans , Mitochondria/genetics , Seroepidemiologic StudiesABSTRACT
Aberrant microRNA expression is involved in the regulation of various cellular processes, such as proliferation and metastasis in multiple diseases including cancers. MicroRNA-30e-5p (miR-30e) was previously reported as an oncogenic or tumour suppressing miRNA in some malignancies, but its function in lung adenocarcinoma (LAC) remains largely undefined. In this study, we found that the expression of miR-30e was increased in LAC tissues and cell lines, associated with tumour size and represented an independent prognostic factor for overall survival and recurrence of LAC patients. Further functional experiments showed that knockdown of miR-30e suppressed cell growth while its overexpression promoted growth of LAC cells and xenografts in vitro and in vivo. Mechanistically, PTPN13 was identified as the direct target of miR-30e in LAC, in which PTPN13 expression was down-regulated in LAC tissues and showed the inverse correlation with miR-30e expression. Overexpression of PTPN13 inhibited cell growth and rescued the proliferation-promoting effect of miR-30e through inhibition of the EGFR signalling. Altogether, our findings suggest that miR-30e could function as an oncogene in LAC via targeting PTPN13 and act as a potential therapeutic target for treating LAC.
Subject(s)
Adenocarcinoma/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , MicroRNAs/genetics , Neoplasm Recurrence, Local/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 13/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma of Lung , Aged , Animals , Cell Line, Tumor , Cell Survival , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Genes, Reporter , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Humans , Lentivirus/genetics , Lentivirus/metabolism , Luciferases/genetics , Luciferases/metabolism , Lung Neoplasms/diagnosis , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Male , Mice, Nude , MicroRNAs/agonists , MicroRNAs/metabolism , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/mortality , Oligoribonucleotides/genetics , Oligoribonucleotides/metabolism , Prognosis , Protein Tyrosine Phosphatase, Non-Receptor Type 13/metabolism , Signal Transduction , Survival Analysis , Xenograft Model Antitumor AssaysABSTRACT
Recurrent aphthous stomatitis (RAS) represents the most common chronic oral diseases with the prevalence ranges from 5% to 25% for different populations. Its pathogenesis remains poorly understood, which limits the development of effective drugs and treatment methods. In this study, we conducted systemic bioinformatics analysis of gene expression profiles from the Gene Expression Omnibus (GEO) to identify potential drug targets for RAS. We firstly downloaded the gene microarray datasets with the accession number of GSE37265 from GEO and performed robust multi-array (RMA) normalization with affy R programming package. Secondly, differential expression genes (DEGs) in RAS samples compared with control samples were identified based on limma package. Enriched gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, protein-protein interaction (PPI) network was constructed based on the combination of HPRD and BioGrid databases. What's more, we identified modules of PPI network through MCODE plugin of Cytoscape for the purpose of screening of valuable targets. As a result, 915 genes were found to be significantly differential expression in RAS samples and biological processes related to immune and inflammatory response were significantly enriched in those genes. Network and module analysis identified FBXO6, ITGA4, VCAM1 and etc as valuable therapeutic targets for RAS. Finally, FBXO6, ITGA4, and VCAM1 were further confirmed by real time RT-PCR and western blot. This study should be helpful for the research and treatment of RAS.
