Project description:MicroRNAs is a rapidly expanding area expected to change the way in which diseases will be diagnosed, treated and monitored in the future. Hepatocellular carcinoma (HCC) shows a rising incidence with high mortality but lack of effective targeted therapies. We identified the aberrantly expressed miRNAs involved in HCC through the comparison of miRNA expression profiling in cancerous hepatocytes with that in normal primary human hepatocytes and found 37 dysregulated miRNAs in HCC. There were 9 up-regulated miRNAs and 28 down-regulated miRNAs in HCC, of which, miR-221 and miR-99b were the most overexpressed miRNAs, while miR-375, miR-192, miR-146b-5p, miR-885-5p, miR-122* and miR-122 were noted for their greatest changes of decreased expression. These aberrantly expressed miRNAs may provide insights into pathogenesis of HCC and thus may be used for diagnosis and therapy.
Project description:MicroRNAs is a rapidly expanding area expected to change the way in which diseases will be diagnosed, treated and monitored in the future. Hepatocellular carcinoma (HCC) shows a rising incidence with high mortality but lack of effective targeted therapies. We identified the aberrantly expressed miRNAs involved in HCC through the comparison of miRNA expression profiling in cancerous hepatocytes with that in normal primary human hepatocytes and found 37 dysregulated miRNAs in HCC. These aberrantly expressed miRNAs may provide insights into pathogenesis of HCC and thus may be used for diagnosis and therapy. Over the past few years, though several studies have uncovered aberrant miRNA expression profiles in HCC compared with matched nonmalignant tissues, the overlap of deregulated miRNAs from different platforms is limited. To solve this problem, we recommend a method that using primary cancer cells or cancer cell lines and nonmalignant primary cells to identify the specific aberrantly miRNA expression profiles in HCC and even in other types of cancer. Here, we identified the aberrantly expressed miRNAs involved in hepatoma through the comparison of miRNA expression profiling in cancerous hepatocytes with that in normal primary human hepatocytes and 37 dysregulated miRNAs were screened out by 2-fold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs whose fold changes were over 15-fold change exhibited significantly differential expression pattern between the cancerous and normal hepatocytes.
Project description:Identification by Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) of ChREBP binding sites in primary cultured mouse hepatocytes cultured for 24h with 25 mM glucose and 100 nM insulin.
Project description:Chronic hepatitis B virus (HBV) infections represent a major global health burden requiring effective therapeutic interventions. This study investigates the antiviral potential of microRNAs (miRNAs) targeting the HBV entry receptor, sodium-taurocholate cotransporting polypeptide (NTCP). Using an experimental model of primary human hepatocytes (PHHs), we highlighted a set of candidate antiviral miRNAs induced by interferon (IFN) alpha analog treatment. Notably, predictive analysis identified miR-29b-1-5p as interacting with the 3’-untranslated region (3’-UTR) of NTCP, suggesting a post-transcriptional regulatory mechanism. Functional analysis indicated that miR-29b-1-5p directly targeted the NTCP 3’-UTR, leading to significant inhibition of NTCP transcripts. Consistently, hepatocytes overexpressing miR-29b-1-5p showed a remarkable reduction in HBV genome levels after infection. A rescue assay demonstrated that miR-29b-1-5p anti-HBV effect was specifically mediated by NTCP targeting. In summary, these findings underscore the therapeutic potential of miR-29b-1-5p against HBV, advocating for further exploration of miRNA-based therapies in the treatment of human viral infections.