HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma.
Oncotarget
; 6(32): 33791-804, 2015 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-26393879
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trans-Activators
/
Carcinoma, Hepatocellular
/
MAP Kinase Signaling System
/
RNA, Long Noncoding
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Hepatitis B Surface Antigens
/
Liver Neoplasms
Type of study:
Prognostic_studies
Limits:
Aged
/
Animals
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Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Oncotarget
Year:
2015
Document type:
Article
Affiliation country:
China