TdIF1: a putative oncogene in NSCLC tumor progression.
TdIF1: a putative oncogene in NSCLC tumor progression.
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TdIF1：NSCLC 肿瘤进展中的假定癌基因
DOI：
10.1038/s41392-018-0030-9
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发表时间：
2018
影响因子：
39.3
通讯作者：
Min W
中科院分区：
文献类型：
--
作者：
Zhang Y;Wang Z;Huang Y;Ying M;Wang Y;Xiong J;Liu Q;Cao F;Joshi R;Liu Y;Xu D;Zhang M;Yuan K;Zhou N;Koropatnick J;Min W
TdT相互作用因子1（TdIF 1）是一种广泛表达的DNA和蛋白质结合蛋白，可直接与末端脱氧核苷酸转移酶（TdT）聚合酶结合。关于TdIF 1在癌症细胞信号传导中的功能作用知之甚少，以前也没有发现它在任何类型的癌症中异常。我们首次报道了TdIF 1在临床肺癌患者中大量表达，并且TdIF 1的高表达与患者预后不良相关。我们进一步确定，与正常肺细胞系相比，TdIF 1在人非小细胞肺癌（NSCLC）细胞系中高度表达。shRNA介导的TdIF 1基因沉默导致A549腺癌细胞系增殖和锚定非依赖性集落形成的抑制。此外，当这些TdIF 1沉默的细胞用于建立人NSCLC的小鼠异种移植模型时，肿瘤大小大大减小。这些数据表明，TdIF 1是肺肿瘤发展的有效调节剂。通过计算机模拟分析，几种细胞周期相关和肿瘤生长信号传导途径，包括p53和HDAC 1/2途径，被鉴定为参与TdIF 1信号传导网络。微阵列、转录组和蛋白水平分析验证了NSCLC细胞模型中TdIF 1下调后p53和HDAC 1/2的调节作用。此外，其他几种细胞周期调节因子在转录水平受到TdIF 1沉默的影响，包括CDKN 1A/p21转录物的增加。总之，这些结果表明TdIF 1是非小细胞肺癌中的一种非肿瘤促进因子，是一种潜在的治疗靶点。
TdT-interacting factor 1 (TdIF1) is a ubiquitously expressed DNA- and protein-binding protein that directly binds to terminal deoxynucleotidyl transferase (TdT) polymerase. Little is known about the functional role of TdIF1 in cancer cellular signaling, nor has it previously been identified as aberrant in any type of cancer. We report here for the first time that TdIF1 is abundantly expressed in clinical lung cancer patients and that high expression of TdIF1 is associated with poor patient prognosis. We further established that TdIF1 is highly expressed in human non-small cell lung cancer (NSCLC) cell lines compared to a normal lung cell line. shRNA-mediated gene silencing of TdIF1 resulted in the suppression of proliferation and anchorage-independent colony formation of the A549 adenocarcinoma cell line. Moreover, when these TdIF1-silenced cells were used to establish a mouse xenograft model of human NSCLC, tumor size was greatly reduced. These data suggest that TdIF1 is a potent regulator of lung tumor development. Several cell cycle-related and tumor growth signaling pathways, including the p53 and HDAC1/2 pathways, were identified as participating in the TdIF1 signaling network by in silico analysis. Microarray, transcriptome and protein-level analyses validated p53 and HDAC1/2 modulation upon TdIF1 downregulation in an NSCLC cellular model. Moreover, several other cell cycle regulators were affected at the transcript level by TdIF1 silencing, including an increase in CDKN1A/p21 transcripts. Taken together, these results indicate that TdIF1 is abona fidetumor-promoting factor in NSCLC and a potential target for therapy.
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影响因子：
46.9
作者：
Bantscheff, Marcus;Hopf, Carsten;Drewes, Gerard
通讯作者：
Drewes, Gerard
影响因子：
2.1
作者：
Hayano, Takahide;Koiwai, Kotaro;Koiwai, Osamu
通讯作者：
Koiwai, Osamu
影响因子：
--
作者：
Kroesen M;Gielen P;Brok IC;Armandari I;Hoogerbrugge PM;Adema GJ
通讯作者：
Adema GJ
影响因子：
56.9
作者：
KOMORI, T;OKADA, A;ALT, FW
通讯作者：
ALT, FW
影响因子：
1.6
作者：
Cao LL;Song X;Pei L;Liu L;Wang H;Jia M
通讯作者：
Jia M