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学科主题: 临床医学
题名:
Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis
作者: Xu, Xiaojie1,2; Fan, Zhongyi1,3; Kang, Lei1,4; Han, Juqiang1,5; Jiang, Chengying1,6; Zheng, Xiaofei7; Zhu, Ziman3; Jiao, Huabo3; Lin, Jing3; Jiang, Kai1; Ding, Lihua1; Zhang, Hao1; Cheng, Long1; Fu, Hanjiang7; Song, Yi7; Jiang, Ying7; Liu, Jiahong1,3; Wang, Rongfu4; Du, Nan3; Ye, Qinong1,2
刊名: JOURNAL OF CLINICAL INVESTIGATION
发表日期: 2013-02-01
DOI: 10.1172/JCI64265
卷: 123, 期:2, 页:630-645
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: EPITHELIAL-MESENCHYMAL TRANSITION ; CANCER-CELL-GROWTH ; HEPATOCELLULAR-CARCINOMA ; SIGNALING PATHWAYS ; BREAST-CANCER ; MTOR ; METASTASIS ; ACTIVATION ; INVASION ; RECEPTOR
英文摘要:

MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and,subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.

语种: 英语
所属项目编号: 2011CB504202 ; 2012CB945100 ; 2009CB521804 ; 81072173 ; 31100604 ; 81101065 ; 30625035 ; 30530320 ; 2009ZX09301-002
项目资助者: Major State Basic Research Development Program ; National Natural Science Foundation ; National Key Technologies R&amp ; D Program for New Drugs
WOS记录号: WOS:000314553600020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67460
Appears in Collections:北京大学第一临床医学院_核医学科_期刊论文

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作者单位: 1.Beijing Mil Gen Hosp, Inst Hepatol, Beijing, Peoples R China
2.Beijing Inst Radiat Med, Beijing, Peoples R China
3.Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing 100850, Peoples R China
4.Dalian Med Univ, Ctr Canc, Inst Canc Stem Cell, Liaoning, Peoples R China
5.Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Beijing, Peoples R China
6.Peking Univ, Dept Nucl Med, Hosp 1, Beijing 100871, Peoples R China
7.Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing, Peoples R China

Recommended Citation:
Xu, Xiaojie,Fan, Zhongyi,Kang, Lei,et al. Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis[J]. JOURNAL OF CLINICAL INVESTIGATION,2013,123(2):630-645.
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