The truncated mutant HBsAg expression increases the tumorigenesis of hepatitis B virus by regulating TGF-β/Smad signaling pathway.
The truncated mutant HBsAg expression increases the tumorigenesis of hepatitis B virus by regulating TGF-β/Smad signaling pathway.
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截短的突变型 HBsAg 表达通过调节 TGF-β/Smad 信号通路增加乙型肝炎病毒的肿瘤发生
DOI：
10.1186/s12985-018-0972-0
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发表时间：
2018-04-02
期刊：
影响因子：
4.8
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Wang ML;Wu DB;Tao YC;Chen LL;Liu CP;Chen EQ;Tang H
研究背景有报道称，HBVrtA181T/sW172*突变株的出现可导致HBs Ag的显性分泌缺陷，增加肝细胞癌的发生风险。本研究旨在揭示HBVrtA181T/sW172*突变株的致瘤作用及可能的致病机制。结果稳定表达突变株的L02细胞克隆形成率明显高于野生型或替换突变株。与稳定表达野生型和替换型HBs Ag的L02细胞相比，将稳定表达截短突变的HBs Ag的L02细胞注射到裸鼠背部皮肤皱褶中，可促进原发肿瘤的生长。在乙肝病毒复制的L02细胞系中，还研究了参与转化生长因子-β/Smad途径的关键分子。研究发现，与稳定表达野生型和替换突变的细胞相比，稳定表达截短突变的乙型肝炎病毒表面抗原的细胞中Smad3/2、CREB和细胞周期蛋白D1mRNA和蛋白水平显著升高，而TGFBI的表达水平显著降低。另外，注射稳定表达截短β的L02细胞后，裸鼠移植瘤体积明显缩小。结论sW172*突变株的出现可能增加了β的致瘤性，其机制可能与其下调TGFF1/Smad信号通路的表达有关。
BackgroundIt has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant.ResultsAs compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg. Injection of L02 cells stable expressing truncated mutant HBsAg into the dorsal skin fold of nude mice resulted in increased primary tumor growth compared to L02 cells stable expressing wide-type and substituted mutant HBsAg. In HBV replication L02 cell lines, the key molecular involved in TGF-β/Smad pathway was also investigated. We found that the mRNA and protein levels of Smad3/2, CREB and CyclinD1 were significantly higher and TGFBI level was significantly lower in cells stably expressing truncated mutant HBsAg as compared to cells stably expressing wide-type and substituted mutant HBsAg. Additionally, after administration of TGF-β1 (increasing TGFBI level), the volume of tumor is obviously reduced in nude mice with injection of L02 cells stable expressing truncated HBsAg.ConclusionsThe emergence of sW172* mutant may increase the tumorigenesis of HBV, and its mechanism may be associated with down-regulated expression of TGFBI in TGF-β/Smad signaling pathway.
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影响因子：
25.7
作者：
Lee, Seoung-Ae;Kim, Kijeong;Kim, Bum-Joon
通讯作者：
Kim, Bum-Joon
影响因子：
13.5
作者：
Warner, Nadia;Locarnini, Stephen
通讯作者：
Locarnini, Stephen
HBsAg表达截短或取代的HBV rtA181T突变体体外和体内模型系统的生物学特性比较
影响因子：
4.6
作者：
Zhou LY;Chen EQ;Wang ML;Chen LL;Liu CP;Zeng F;Tang H
通讯作者：
Tang H
影响因子：
4.8
作者：
Dai J;Chen EQ;Bai L;Gong DY;Zhou QL;Cheng X;Huang FJ;Tang H
通讯作者：
Tang H
影响因子：
4.2
作者：
Deng, Lihui;Tang, Hong
通讯作者：
Tang, Hong