Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma
Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma
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Fra-1 调节 HMGA1 的表达，HMGA1 与人食管鳞状细胞癌的不良预后相关
DOI：
10.1245/s10434-016-5666-5
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发表时间：
2017
影响因子：
3.7
通讯作者：
H. Matsubara
中科院分区：
文献类型：
--
作者：
Takeshi Toyozumi;Isamu Hoshino;Masahiko Takahashi;A. Usui;Y. Akutsu;N. Hanari;Kentaro Murakami;M. Kano;Naoki Akanuma;Hiroshi Suitoh;Y. Matsumoto;N. Sekino;Aki Komatsu;H. Matsubara
背景Fos相关抗原1（Fra-1）的表达影响肿瘤的进展、迁移和侵袭。本研究通过转染小干扰RNA（small interfering RNA，siRNA）构建食管鳞癌细胞株（TE 10，TE 11）中Fra-1基因的敲低模型，并对Fra-1基因在食管鳞癌中的表达进行研究。使用微阵列和Biobase上游分析法分析敲除模型中基因的表达水平，而使用实时聚合酶链反应（PCR）和免疫组织化学染色法测定从ESCC患者获得的手术标本的原发肿瘤中候选基因的表达水平。结果生物碱基上游分析表明，高迁移率族蛋白1（HMGA 1）是一个重要的基因调控的Fra-1。在随后的染色质免疫沉淀PCR实验中揭示了Fra-1与HMGA 1启动子区域的实际结合。结论HMGA 1在食管鳞癌中的表达受Fra-1的调控，HMGA 1的表达与食管鳞癌患者的预后密切相关。下调HMGA 1表达可能成为未来食管鳞癌的一种实用治疗策略。
BackgroundThe expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC).MethodsWe constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed.ResultsThe Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor.ConclusionHMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.
高迁移率族蛋白 HMGI(Y) 的表达与 Barrett 化生的恶性进展相关。
DOI：
10.1158/1055-9965.epi-03-0151
发表时间：
2004
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Chen,Xueyun;Lechago,Juan;Ertan,Atilla;Ergun,Gulchin;Verm,Ray;Bridges,Margaret;Johnson,Craig;Woods,Karen;Meriano,Frank;Chirala,Minni;Younes,Mamoun
通讯作者：
Younes,Mamoun
DOI：
10.1165/rcmb.2004-0198oc
发表时间：
2005-01-01
影响因子：
6.4
作者：
Zhang, Q;Adiseshaiah, P;Reddy, SP
通讯作者：
Reddy, SP