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- Title
HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells.
- Authors
Xiao-xiao Kong; Yan-ru Lv; Li-ping Shao; Xiang-yang Nong; Guang-ling Zhang; Yi Zhang; Hong-xia Fan; Min Liu; Xin Li; Hua Tang; Kong, Xiao-Xiao; Lv, Yan-Ru; Shao, Li-Ping; Nong, Xiang-Yang; Zhang, Guang-Ling; Zhang, Yi; Fan, Hong-Xia; Liu, Min; Li, Xin; Tang, Hua
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
CELL proliferation; HEPATOCELLULAR carcinoma; HEPATITIS B virus; POLYMERASE chain reaction; FLOW cytometry; CARCINOGENESIS
- Publication
Journal of Translational Medicine, 2016, Vol 14, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-016-0949-y