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- Title
TdIF1: a putative oncogene in NSCLC tumor progression.
- Authors
Zhang, Yujuan; Wang, Zhigang; Huang, Yanqing; Ying, Muying; Wang, Yifan; Xiong, Juan; Liu, Qi; Cao, Fan; Joshi, Rakesh; Liu, Yanling; Xu, Derong; Zhang, Meng; Yuan, Keng; Zhou, Nanjin; Koropatnick, James; Min, Weiping
- Abstract
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 a bona fide tumor-promoting factor in NSCLC and a potential target for therapy. Immune protein involved in lung cancer: A protein involved in the immune system also plays a role in the most common type of lung cancer. Weiping Min, of the University of Western Ontario in Canada, and international colleagues found, for the first time, that the protein TdIF1 is significantly upregulated in non-small cell lung cancer (NSCLC) tissues in patients. High expression levels of this protein were correlated with poor prognosis. NSCLC tumor tissues grown in mice where TdIF1 expression was 'knocked down' were significantly smaller than in those without TdIF1 knockdown. Further analyses showed the protein was involved in known cell signaling pathways with roles in NSCLC progression. The findings indicate TdIF1 should be further investigated as a biomarker of NSCLC or as a molecular target for its treatment.
- Publication
Signal Transduction & Targeted Therapy, 2018, Vol 3, Issue 1, pN.PAG
- ISSN
2095-9907
- Publication type
Article
- DOI
10.1038/s41392-018-0030-9