ArticlePloS one2012
Genome-wide analyses of Nkx2-1 binding to transcriptional target genes uncover novel regulatory patterns conserved in lung development and tumors.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
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- The role of homeobox genes in signaling pathway positive feedback loops and cancer therapy.Frontiers in oncology · 2026Article
- Perturbation of the circadian clock in chronic diseases involving organ fibrosis.The Journal of clinical investigation · 2025Review
- Defining cis-regulatory elements and transcription factors that control human cortical interneuron development.iScience · 2024Article
- Significance ofPeerJ · 2024Article
- Metastasis Inhibition.International journal of molecular sciences · 2023Article
- Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer.Journal of clinical medicine · 2022Article
- The homeodomain transcription factor Ventx2 regulates respiratory progenitor cell number and differentiation timing during Xenopus lung development.Development, growth & differentiation · 2022Article
- RNA-Sequencing approach for exploring the therapeutic effect of umbilical cord mesenchymal stem/stromal cells on lipopolysaccharide-induced acute lung injury.Frontiers in immunology · 2022Article
- Deciphering an isolated lung phenotype of NKX2-1 frameshift pathogenic variant.Frontiers in pediatrics · 2022Article
- NKX6-1 mediates cancer stem-like properties and regulates sonic hedgehog signaling in leiomyosarcoma.Journal of biomedical science · 2021Article
- Thyroid Transcription Factor-1: Structure, Expression, Function and Its Relationship with Disease.BioMed research international · 2021Review
- NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer.International journal of molecular sciences · 2020Article
- Delineating the early transcriptional specification of the mammalian trachea and esophagus.eLife · 2020Article
- It's about time: clocks in the developing lung.The Journal of clinical investigation · 2020Review
- Transcriptional control of lung alveolar type 1 cell development and maintenance by NK homeobox 2-1.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Encapsulated miR-200c and Nkx2.1 in a nuclear/mitochondria transcriptional regulatory network of non-metastatic and metastatic lung cancer cells.BMC cancer · 2019Article
- NKX2-1-AS1 negatively regulates CD274/PD-L1, cell-cell interaction genes, and limits human lung carcinoma cell migration.Scientific reports · 2018Article
- Mutations in the thyroid transcription factor gene NKX2-1 result in decreased expression of SFTPB and SFTPC.Pediatric research · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The homeodomain transcription factor Nkx2-1 is essential for normal lung development and homeostasis. In lung tumors, it is considered a lineage survival oncogene and prognostic factor depending on its expression levels. The target genes directly bound by Nkx2-1, that could be the primary effectors of its functions in the different cellular contexts where it is expressed, are mostly unknown. In embryonic day 11.5 (E11.5) mouse lung, epithelial cells expressing Nkx2-1 are predominantly expanding, and in E19.5 prenatal lungs, Nkx2-1-expressing cells are predominantly differentiating in preparation for birth. To evaluate Nkx2-1 regulated networks in these two cell contexts, we analyzed genome-wide binding of Nkx2-1 to DNA regulatory regions by chromatin immunoprecipitation followed by tiling array analysis, and intersected these data to expression data sets. We further determined expression patterns of Nkx2-1 developmental target genes in human lung tumors and correlated their expression levels to that of endogenous NKX2-1. In these studies we uncovered differential Nkx2-1 regulated networks in early and late lung development, and a direct function of Nkx2-1 in regulation of the cell cycle by controlling the expression of proliferation-related genes. New targets, validated in Nkx2-1 shRNA transduced cell lines, include E2f3, Cyclin B1, Cyclin B2, and c-Met. Expression levels of Nkx2-1 direct target genes identified in mouse development significantly correlate or anti-correlate to the levels of endogenous NKX2-1 in a dosage-dependent manner in multiple human lung tumor expression data sets, supporting alternative roles for Nkx2-1 as a transcriptional activator or repressor, and direct regulator of cell cycle progression in development and tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.