Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study.

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study.
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TRAF6 与 HCC 恶化之间的关系:免疫组织化学和体外研究

DOI:
10.1186/s12935-016-0352-z
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发表时间:
2016
影响因子:
5.8
通讯作者:
Chen G
Chen G
中科院分区:
医学2区
文献类型:
--
作者:
Li JJ;Luo J;Lu JN;Liang XN;Luo YH;Liu YR;Yang J;Ding H;Qin GH;Yang LH;Dang YW;Yang H;Chen G

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目的探讨肿瘤坏死因子受体相关因子6(TRAF 6)与肝细胞癌(HCC)临床病理特征的关系及其生物学功能。免疫组化法检测TRAF 6的表达。分析TRAF 6表达与HCC临床病理参数的相关性。进一步通过体外实验验证TRAF 6对肝癌细胞的生物学功能。将TRAF 6 siRNA转染到HepG 2和Hep 3B细胞系中,并通过RT-qPCR和western blot评估TRAF 6表达。采用RNA干扰技术检测TRAF 6对肝癌细胞存活率、增殖、凋亡及caspase-3/7活性的影响。用Cell Titer-Blue试剂盒评估细胞活力。MTS试剂盒检测细胞增殖。结果TRAF 6蛋白在肝癌组织中的阳性表达率为49.7%,显著高于正常肝组织(12.1%)、肝硬化组织(21.6%)和癌旁组织(36.3%)(P均< 0.05)。TRAF 6在转移组(Z = − 2.058,P = 0.04)和微血管密度(MVD)低表达组(Z = − 2.813,P = 0.005)中表达上调。斯皮尔曼相关分析进一步显示TRAF 6的表达与远处转移呈正相关(r = 0.158,P = 0.039),与MVD呈负相关(r =-0.249,P = 0.004)。结论TRAF 6可能通过影响肝癌细胞的生长和凋亡,参与肝癌的转移和恶化。因此,TRAF 6可能成为HCC的预测和治疗生物标志物。
ObjectiveTo explore the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and the clinicopathological features in HCC as well as its biological function.MethodsTotally, 412 liver tissues were collected, including 171 hepatocellular carcinoma (HCC) and their corresponding non-tumor tissues, 37 cirrhosis and 33 normal liver tissues. The expression of TRAF6 was assessed by immunohistochemistry. Then, analysis of the correlations between TRAF6 expression and clinicopathological parameters in HCC was conducted. Furtherer, in vitro experiments on HepG2 and Hep3B cells were performed to validate the biological function of TRAF6 on HCC cells. TRAF6 siRNA was transfected into HepG2 and Hep3B cell lines and TRAF6 expression was evaluated with RT-qPCR and western blot. The assays of cell viability, proliferation, apoptosis and caspase-3/7 activity were carried out to investigate the effects of TRAF6 on HCC cells with RNA interference. Cell viability was assessed with Cell Titer-Blue kit. Cell proliferation was tested with MTS kit. Cell apoptosis was checked through morphologic detection with fluorescence microscope, as well as caspase-3/7 activity was measured with fluorogenic substrate detection.ResultsThe positive expression rate of TRAF6 protein was 49.7 % in HCC, significantly higher than that of normal liver (12.1 %), cirrhosis (21.6 %) and adjacent non-cancerous tissues (36.3 %, allP< 0.05). Upregulated TRAF6 was detected in groups with metastasis (Z = −2.058,P= 0.04) and with low micro-vessel density (MVD) expression (Z = −2.813,P= 0.005). Spearman correlation analysis further showed that the expression of TRAF6 was positively correlated with distant metastasis (r = 0.158,P= 0.039) and negatively associated with MVD (r = −0.249,P= 0.004). Besides, knock-down of TRAF6 mRNA in HCC cell lines HepG2 and Hep3B both resulted in cell viability and proliferation inhibition, also cell apoptosis induction and caspase-3/7 activity activation.ConclusionsTRAF6 may contribute to metastasis and deterioration of the HCC via influencing cell growth and apoptosis. Thus, TRAF6 might become a predictive and therapeutic biomarker for HCC.
DOI: 10.1186/s12935-015-0214-0
发表时间: 2015
影响因子: 5.8
作者:
Liu Y;Ren F;Rong M;Luo Y;Dang Y;Chen G
通讯作者: Chen G
DOI: 10.3748/wjg.v20.i20.6236
发表时间: 2014-05-28
影响因子: 4.3
作者:
Hai, Hoang;Tamori, Akihiro;Kawada, Norifumi
通讯作者: Kawada, Norifumi
TRAF6在结肠癌中表达上调并促进结肠癌细胞增殖
DOI: 10.1016/j.biocel.2014.04.010
发表时间: 2014-08-01
影响因子: 4
作者:
Sun, Heng;Li, Xuebing;Fang, Jing
通讯作者: Fang, Jing
DOI: 10.1016/j.canlet.2015.05.025
发表时间: 2015-09-01
期刊: CANCER LETTERS
影响因子: 9.7
作者:
Chiu, Hui-Wen;Lin, Shu-Wen;Wang, Ying-Jan
通讯作者: Wang, Ying-Jan
DOI: 10.1172/jci58818
发表时间: 2011-10-01
影响因子: 15.9
作者:
Starczynowski, Daniel T.;Lockwood, William W.;Karsan, Aly
通讯作者: Karsan, Aly