HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells
| Autor: | Hongxia Fan, Yi Zhang, Yan-ru Lv, Xin Li, Xiao-xiao Kong, Min Liu, Li-ping Shao, Guang-ling Zhang, Hua Tang, Xiang-Yang Nong |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Transcription Genetic Cell Cycle Proteins medicine.disease_cause NF-κB chemistry.chemical_compound Cell Movement Viral Regulatory and Accessory Proteins HCC Promoter Regions Genetic 3' Untranslated Regions Medicine(all) Cell Cycle Liver Neoplasms NF-kappa B Hep G2 Cells General Medicine CDC40 Cell cycle Up-Regulation Gene Expression Regulation Neoplastic HBx Phenotype Hepatocellular carcinoma RNA Splicing Factors miR-1269b Protein Binding Carcinoma Hepatocellular Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences microRNA medicine Humans neoplasms Cell Proliferation Hepatitis B virus Base Sequence Cell growth Biochemistry Genetics and Molecular Biology(all) Research medicine.disease NFKB1 Virology digestive system diseases MicroRNAs 030104 developmental biology chemistry Trans-Activators Cancer research |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| DOI: | 10.1186/s12967-016-0949-y |
| Popis: | Background Occurrence and progression of hepatocellular carcinoma (HCC) are associated with hepatitis B virus (HBV) infection. miR-1269b is up-regulated in HCC cells and tissues. However, the regulation of miR-1269b expression by HBV and the mechanism underlying the oncogenic activity of miR-1269b in HCC are unclear. Methods Reverse transcription quantitative PCR (RT-qPCR) was used to measure the expression of miR-1269b and target genes in HCC tissues and cell lines. Western blot analysis was used to assess the expression of miR-1269b target genes and related proteins. Using luciferase reporter assays and EMSA, we identified the factors regulating the transcriptional level of miR-1269b. Colony formation, flow cytometry and cell migration assays were performed to evaluate the phenotypic changes caused by miR-1269b and its target in HCC cells. Results We demonstrated that the expression levels of pre-miR-1269b and miR-1269b in HBV-positive HepG2.2.15 cells were dramatically increased compared with HBV-negative HepG2 cells. HBx was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB binds to the promoter of miR-1269b to enhance its transcription. miR-1269b targets and up-regulates CDC40, a cell division cycle 40 homolog. CDC40 increases cell cycle progression, cell proliferation and migration. Rescue experiment indicated that CDC40 promotes malignancy induced by miR-1269b in HCC cells. Conclusion We found that HBx activates NF-κB to promote the expression of miR1269b, which augments CDC40 expression, contributing to malignancy in HCC. Our findings provide insights into the mechanisms underlying HBV-induced hepatocarcinogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|