Loss of RUNX1 is associated with aggressive lung adenocarcinomas.
Loss of RUNX1 is associated with aggressive lung adenocarcinomas.
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DOI：
10.1002/jcp.26201
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发表时间：
2018-04
影响因子：
5.6
通讯作者：
Kinsey CM
中科院分区：
文献类型：
--
作者：
Ramsey J;Butnor K;Peng Z;Leclair T;van der Velden J;Stein G;Lian J;Kinsey CM
哺乳动物矮小相关因子1 （RUNX1）是调节造血干细胞谱系规范的主转录因子。RUNX1易位导致髓性白血病的发生。最近，RUNX1在其他癌症中被认为是肿瘤抑制因子。我们假设RUNX1的表达可能与肺腺癌的病因和/或进展有关。我们评估了RUNX1 mRNA表达与癌症基因组图谱（TCGA）中总生存数据的关系，TCGA是一个公开的数据库。与高表达水平相比，肺腺癌中RUNX1的低表达水平与较差的总生存率相关（风险比= 2.014(95%置信区间为1.042至3.730),log-rank P=0.035）。对佛蒙特大学医学中心切除的85例手术标本的进一步免疫组织化学检查发现，RUNX1蛋白的低表达与较大的肿瘤有关（P=0.038）。基因表达网络分析对通过RUNX1表达表现出差异生存的TCGA病例的同一亚群进行。该分析揭示了调控关系，表明RUNX1水平的降低与转录因子E2F1的上调密切相关。为了探究这种关系，在表达高水平RUNX1的肺癌细胞系中，RUNX1被耗尽。RUNX1的缺失导致增殖、迁移和侵袭增强。RUNX1缺失也导致E2F1和多个E2F1靶基因mRNA表达增加。我们的数据暗示RUNX1作为肺腺癌侵袭的驱动因素的缺失，可能通过E2F1通路的解除管制。
The mammalian runt-related factor 1 (RUNX1) is a master transcription factor that regulates lineage specification of hematopoietic stem cells. RUNX1 translocations result in the development of myeloid leukemias. Recently, RUNX1 has been implicated as a tumor suppressor in other cancers. We postulated RUNX1 expression may be associated with lung adenocarcinoma etiology and/or progression. We evaluated the association of RUNX1 mRNA expression with overall survival data from The Cancer Genome Atlas (TCGA), a publically available database. Compared to high expression levels, Low RUNX1 levels from lung adenocarcinomas were associated with a worse overall survival (Hazard Ratio = 2.014 (1.042 to 3.730 95% confidence interval), log-rank P=0.035) compared to those that expressed high RUNX1 levels. Further immunohistochemical examination of 85 surgical specimens resected at the University of Vermont Medical Center identified that low RUNX1 protein expression was associated with larger tumors (P=0.038). Gene expression network analysis was performed on the same subset of TCGA cases that demonstrated differential survival by RUNX1 expression. This analysis, which reveals regulatory relationships, showed that reduced RUNX1 levels were closely linked to upregulation of the transcription factor E2F1. To interrogate this relationship, RUNX1 was depleted in a lung cancer cell line that expresses high levels of RUNX1. Loss of RUNX1 resulted in enhanced proliferation, migration, and invasion. RUNX1 depletion also resulted in increased mRNA expression of E2F1 and multiple E2F1 target genes. Our data implicate loss of RUNX1 as driver of lung adenocarcinoma aggression, potentially through deregulation of the E2F1 pathway.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
--
作者：
Hong D;Messier TL;Tye CE;Dobson JR;Fritz AJ;Sikora KR;Browne G;Stein JL;Lian JB;Stein GS
通讯作者：
Stein GS
DOI：
10.2741/3977
发表时间：
2012-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Lam K;Zhang DE
通讯作者：
Zhang DE
影响因子：
--
作者：
Farina NH;Zingiryan A;Akech JA;Callahan CJ;Lu H;Stein JL;Languino LR;Stein GS;Lian JB
通讯作者：
Lian JB
影响因子：
45.3
作者：
Camp, Robert L.;Neumeister, Veronique;Rimm, David L.
通讯作者：
Rimm, David L.