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HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma.
Oncotarget 2015; 6(32):33791-804O

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.

Authors+Show Affiliations

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Department of Neurosurgery, Fujian Provincial Hospital, Fuzhou, Fujian, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26393879

Citation

Huang, Jin-lan, et al. "HBx-related Long Non-coding RNA DBH-AS1 Promotes Cell Proliferation and Survival By Activating MAPK Signaling in Hepatocellular Carcinoma." Oncotarget, vol. 6, no. 32, 2015, pp. 33791-804.
Huang JL, Ren TY, Cao SW, et al. HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget. 2015;6(32):33791-804.
Huang, J. L., Ren, T. Y., Cao, S. W., Zheng, S. H., Hu, X. M., Hu, Y. W., ... Wang, Q. (2015). HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget, 6(32), pp. 33791-804. doi:10.18632/oncotarget.5667.
Huang JL, et al. HBx-related Long Non-coding RNA DBH-AS1 Promotes Cell Proliferation and Survival By Activating MAPK Signaling in Hepatocellular Carcinoma. Oncotarget. 2015 Oct 20;6(32):33791-804. PubMed PMID: 26393879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. AU - Huang,Jin-lan, AU - Ren,Ting-yu, AU - Cao,Shun-wang, AU - Zheng,Shi-hao, AU - Hu,Xiu-mei, AU - Hu,Yan-wei, AU - Lin,Li, AU - Chen,Jing, AU - Zheng,Lei, AU - Wang,Qian, PY - 2015/03/04/received PY - 2015/08/23/accepted PY - 2015/9/23/entrez PY - 2015/9/24/pubmed PY - 2016/8/23/medline KW - DBH-AS1 KW - HBx KW - HCC KW - lncRNA KW - proliferation SP - 33791 EP - 804 JF - Oncotarget JO - Oncotarget VL - 6 IS - 32 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/26393879/HBx_related_long_non_coding_RNA_DBH_AS1_promotes_cell_proliferation_and_survival_by_activating_MAPK_signaling_in_hepatocellular_carcinoma_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=5667 DB - PRIME DP - Unbound Medicine ER -