HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma
| Autor: | Xiumei Hu, Qian Wang, Jin-Lan Huang, Shun-wang Cao, Jing Chen, Shi-hao Zheng, Ting-Yu Ren, Yan-Wei Hu, Lei Zheng, Li Lin |
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| Rok vydání: | 2015 |
| Předmět: |
Male
MAPK/ERK pathway Carcinoma Hepatocellular Cell Survival MAP Kinase Signaling System proliferation Down-Regulation Mice Nude Apoptosis Small hairpin RNA Mice lncRNA Downregulation and upregulation RNA interference Cell Line Tumor Animals Humans Viral Regulatory and Accessory Proteins HCC Aged Cell Proliferation Mice Inbred BALB C Hepatitis B Surface Antigens biology Cell growth Cell Cycle Liver Neoplasms Hep G2 Cells Middle Aged Cell cycle digestive system diseases Gene Expression Regulation Neoplastic HBx Cell Transformation Neoplastic Oncology DBH-AS1 Trans-Activators Cancer research biology.protein Female RNA Interference RNA Long Noncoding Cyclin-dependent kinase 6 Tumor Suppressor Protein p53 Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.5667 |
| Popis: | Accumulating evidence supports an important role for the hepatitis B virus x protein (HBx) in the pathogenesis of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC), but the underlying mechanisms are not entirely clear. Here, we identified a novel long noncoding RNA (lncRNA) DBH-AS1 involved in the HBx-mediated hepatocarcinogenesis. The levels of DBH-AS1 were positively correlated with hepatitis B surface antigen (HBsAg) and tumor size in HCC tissues. Functionally, transgenic expression of DBH-AS1 significantly enhanced cell proliferation and tumorigenesis, whereas short hairpin RNA knockdown of DBH-AS1 caused an inhibition of cell proliferation. Mechanistically, overexpression of DBH-AS1 induced cell cycle progression by accelerating G1/S and G2/M transition concomitantly with upregulation of CDK6, CCND1, CCNE1 and downregulation of p16, p21 and p27. We also found that enhanced DBH-AS1 expression inhibited serum starvation-induced apoptosis of HCC cells. In contrast, suppressed DBH-AS1 expression had opposite effects. Furthermore, DBH-AS1 was shown to activate MAPK pathway. We also provide evidence that DBH-AS1 could be significantly induced by HBx protein and markedly down-regulated by p53. Thus, we concluded that DBH-AS1 can be induced by HBx and inactivated by p53, and consequently promote cell proliferation and cell survival through activation of MAPK signaling in HCC. Our study suggests that DBH-AS1 acts as an oncogene for HCC. |
| Databáze: | OpenAIRE |
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