Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer.
Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer.
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评估膀胱癌病理学图集鉴定的预后基因的生物学功能。
DOI：
10.3892/or.2020.7853
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发表时间：
2021-01
期刊：
影响因子：
4.2
通讯作者：
Jiao W
中科院分区：
文献类型：
--
作者：
Chen Y;Xu T;Xie F;Wang L;Liang Z;Li D;Liang Y;Zhao K;Qi X;Yang X;Jiao W
基于癌症基因组图谱数据的病理图谱项目对膀胱癌预后相关基因进行了系统的研究。然而，大多数基因在膀胱癌中的生物学功能尚不清楚。本研究研究了病理学图谱项目报道的12个最重要的生存相关基因（ABRACL、MITD1、ZNF524、EMP1、HSPB6、xorf38、TRIM38、ZNF182、ZNF195、SPRN、PTPN6和LIPT1）在尿路上皮癌中细胞增殖和迁移的生物学功能。在体外，转染12个预后基因后，对T24细胞进行增殖和迁移分析。结果用一个小干扰（si）RNA文库进行了验证。对临床样本进行免疫组化（IHC）分析，以确定基因表达与肿瘤转移的关系。此外，RNA测序用于研究下游信号。在12个预后基因中，转染MIT-domain protein 1 （MITD1）可一定程度抑制T24细胞迁移。用7基因siRNA文库进行的实验表明，MITD1敲低显著上调了细胞的迁移能力。在机制上，通过RNA测序评估MITD1对细胞信号转导的影响。细胞迁移相关基因，包括KISS1、SPANXB1、SPINT1、PIWIL2、SNAI1、APLN和CTHRC1出现异常。免疫组化分析显示，MITD1蛋白在转移淋巴结中的表达明显低于原发肿瘤。综上所述，本研究结果提示预后基因MITD1可能作为一种迁移抑制剂，并可作为改善膀胱癌预后的潜在治疗靶点。
The prognosis-associated genes of urinary bladder cancer have been systematically investigated in the Pathology Atlas project based on The Cancer Genome Atlas data. However, the biological functions of most genes in bladder cancer remain unknown. The present study investigated the biological function of 12 of the most significant survival-associated genes (ABRACL, MITD1, ZNF524, EMP1, HSPB6, CXorf38, TRIM38, ZNF182, ZNF195, SPRN, PTPN6 and LIPT1) in urothelial cancer reported by the Pathology Atlas project, with respect to cell proliferation and migration. In vitro, proliferation and migration analyses of T24 cells were performed following the transfection of the 12 prognostic genes. The results were validated with a small interfering (si)RNA library. Immunohistochemistry (IHC) analysis of clinical samples was performed to determine the association between gene expression and tumor metastasis. Furthermore, RNA sequencing was used to investigate the downstream signals. Among the 12 prognostic genes, MIT-domain containing protein 1 (MITD1) transfection was demonstrated to inhibit T24 cell migration to a certain degree. Experiments performed with a 7-gene siRNA library demonstrated that MITD1 knockdown markedly upregulated cell migratory abilities. Mechanistically, the influence of MITD1 on cell signal transduction was assessed via RNA sequencing. Cell migration-associated genes, including KISS1, SPANXB1, SPINT1, PIWIL2, SNAI1, APLN and CTHRC1 were dysregulated. IHC analysis demonstrated that MITD1 protein expression was notably lower in metastatic lymph nodes compared with the primary tumors. Taken together, the results of the present study suggest that the prognostic gene, MITD1 may serve as a migration inhibitor, and be developed as a potential therapeutic target for improving the prognosis of bladder cancer.
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影响因子：
5.6
作者：
Sun, Yu;Luo, Jiping;Ke, Zunfu
通讯作者：
Ke, Zunfu
影响因子：
11.2
作者：
Harada, Yosuke;Kanehira, Mitsugu;Katagiri, Toyomasa
通讯作者：
Katagiri, Toyomasa
影响因子：
16.6
作者：
Eifler K;Cuijpers SAG;Willemstein E;Raaijmakers JA;El Atmioui D;Ovaa H;Medema RH;Vertegaal ACO
通讯作者：
Vertegaal ACO
影响因子：
10.3
作者：
Lee, JH;Miele, ME;Welch, DR
通讯作者：
Welch, DR
DOI：
10.1016/j.urolonc.2011.02.011
发表时间：
2013-05-01
影响因子：
2.7
作者：
Kassouf, Wassim;Svatek, Robert S.;Skinner, Eila C.
通讯作者：
Skinner, Eila C.