Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.
Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.
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TRIM28 对肿瘤细胞中癌症/睾丸抗原 MAGEC2 表达的转录后调节
DOI：
10.1186/s12885-018-4844-1
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发表时间：
2018-10-11
期刊：
影响因子：
3.8
通讯作者：
Yin Y
中科院分区：
文献类型：
--
作者：
Song X;Guo C;Zheng Y;Wang Y;Jin Z;Yin Y
背景癌/睾丸抗原MAGEC 2（也称为HCA 587）在多种肿瘤中高度表达，在促进肿瘤细胞的生长和转移中起积极作用。然而，很少有人知道MAGEC 2在癌细胞中的表达调控。方法采用Western blotting和定量RT-PCR分析MAGEC 2的表达。采用免疫共沉淀法检测MAGEC 2和TRIM 28在肿瘤细胞中的内源性相互作用。采用过表达和敲低实验检测TRIM 28对MAGEC 2蛋白表达的影响。在肝细胞癌患者中进行免疫组织化学（IHC）染色以评估MAGEC 2和TRIM 28的表达之间的关联。蛋白酶体抑制剂MG 132或PS-341和溶酶体抑制剂氯喹（CQ）被用来抑制蛋白酶体或溶酶体介导的蛋白degradationallowed.ResultsWe表明，MAGEC 2与TRIM 28在黑色素瘤细胞和MAGEC 2在肿瘤细胞中的表达依赖于TRIM 28的表达。当TRIM 28在肿瘤细胞中耗尽时，MAGEC 2蛋白的表达水平显著降低，并且没有观察到MAGEC 2 mRNA水平的变化。此外，MAGEC 2和TRIM 28的表达水平在MAGEC 2阳性人肝细胞癌组织中呈正相关（p= 0.0011）。结论TRIM 28对肿瘤细胞MAGEC 2蛋白表达的调控作用是通过蛋白酶体介导的途径实现的，TRIM 28可能成为肿瘤免疫治疗的新靶点。
BackgroundCancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells.MethodsWestern blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells. Overexpression and knockdown assays were used to examine the effects of TRIM28 on the expression of MAGEC2 protein. Immunohistochemistry (IHC) staining was performed in hepatocellular carcinoma patients to evaluate the association between the expression of MAGEC2 and TRIM28. Proteasome inhibitors MG132 or PS-341 and lysosome inhibitor Chloroquine (CQ) were used to inhibit proteasomal or lysosomal-mediated protein degradation respectively.ResultsWe demonstrate that MAGEC2 interacts with TRIM28 in melanoma cells and MAGEC2 expression in tumor cells depends on the expression of TRIM28. The expression level of MAGEC2 protein was significantly reduced when TRIM28 was depleted in tumor cells, and no changes were observed in MAGEC2 mRNA level. Furthermore, expression levels of MAGEC2 and TRIM28 are positively correlated in MAGEC2-positive human hepatocellular carcinoma tissues (p= 0.0011). Mechanistic studies indicate that the regulatory role of TRIM28 on MAGEC2 protein expression in tumor cells depends on proteasome-mediated pathway.ConclusionsOur findings show that TRIM28 is necessary for MAGEC2 expression in cancer cells, and TRIM28 may serve as a new potential target for immunotherapy of cancer.
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影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
用 CpG 和 ISCOM 配制的 HCA587 蛋白在小鼠中诱导 HCA587 特异性抗肿瘤免疫
影响因子：
3.7
作者：
Chen J;Zhang L;Wen W;Hao J;Zeng P;Qian X;Zhang Y;Yin Y
通讯作者：
Yin Y
影响因子：
10.5
作者：
Friedman, JR;Fredericks, WJ;Rauscher, FJ
通讯作者：
Rauscher, FJ
DOI：
10.4331/wjbc.v5.i3.308
发表时间：
2014-08-26
期刊：
World journal of biological chemistry
影响因子：
--
作者：
Cheng, Chun-Ting;Kuo, Ching-Ying;Ann, David K
通讯作者：
Ann, David K
影响因子：
10.5
作者：
Cammas, F;Herzog, M;Losson, R
通讯作者：
Losson, R