Research Papers:

HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma

Jin-lan Huang _, Ting-yu Ren, Shun-wang Cao, Shi-hao Zheng, Xiu-mei Hu, Yan-wei Hu, Li Lin, Jing Chen, Lei Zheng and Qian Wang

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Oncotarget. 2015; 6:33791-33804. https://doi.org/10.18632/oncotarget.5667

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Jin-lan Huang1,*, Ting-yu Ren1,*, Shun-wang Cao1, Shi-hao Zheng2, Xiu-mei Hu1, Yan-wei Hu1, Li Lin1, Jing Chen1, Lei Zheng1 and Qian Wang1

1 Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

2 Department of Neurosurgery, Fujian Provincial Hospital, Fuzhou, Fujian, China

* These authors have contributed equally to this work

Correspondence to:

Qian Wang, email:

Lei Zheng, email:

Keywords: lncRNA, DBH-AS1, HCC, proliferation, HBx

Received: March 04, 2015 Accepted: August 23, 2015 Published: September 15, 2015


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.

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