Journal article
Identification of novel TGF-beta regulated genes with pro-migratory roles
Biochimica et biophysica acta. Molecular basis of disease, Vol.1865(12), pp.165537-165537
12/01/2019
DOI: 10.1016/j.bbadis.2019.165537
PMID: 31449970
Abstract
Transforming growth factor-beta (TGF-beta) signaling plays fundamental roles in the development and homeostasis of somatic cells. Dysregulated TGF-beta signaling contributes to cancer progression and relapse to therapies by inducing epithelial-to-mesenchymal transition (EMT), enriching cancer stem cells, and promoting immunosuppression. Although many TGF-beta-regulated genes have been identified, only a few datasets were obtained by next-generation sequencing. In this study, we performed RNA-sequencing analysis of MCF10A cells and identified 1166 genes that were upregulated and 861 genes that were downregulated by TGF-beta. Gene set enrichment analysis revealed that focal adhesion and metabolic pathways were the top enriched pathways of the up- and downregulated genes, respectively. Genes in these pathways also possess significant predictive value for renal cancers. Moreover, we confirmed that TGF-beta induced expression of MICAL1 and 2, and the histone demethylase, KDM7A, and revealed their regulatory roles on TGF-beta-induced cell migration. We also show a critical effect of KDM7A in regulating the acetylation of H3K27 on TGF-beta-induced genes. In sum, this study identified novel effectors that mediate the pro-migratory role of TGF-beta signaling, paving the way for future studies that investigate the function of MICAL family members in cancer and the novel epigenetic mechanisms downstream TGF-beta signaling.
Details
- Title: Subtitle
- Identification of novel TGF-beta regulated genes with pro-migratory roles
- Creators
- Qi Liu - Roy J. and Lucille A. Carver College of MedicineNicholas Borcherding - Roy J. and Lucille A. Carver College of MedicinePeng Shao - Roy J. and Lucille A. Carver College of MedicineHuojun Cao - Roy J. and Lucille A. Carver College of MedicineWeizhou Zhang - Roy J. and Lucille A. Carver College of MedicineHank Heng Qi - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Molecular basis of disease, Vol.1865(12), pp.165537-165537
- DOI
- 10.1016/j.bbadis.2019.165537
- PMID
- 31449970
- NLM abbreviation
- Biochim Biophys Acta Mol Basis Dis
- ISSN
- 0925-4439
- eISSN
- 1879-260X
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- P30CA086862 / Holden Comprehensive Cancer Center, University of Iowa 01-224 / Roy J. Carver Charitable Trust CA200673; CA203834; P30 CA086862; F30 CA206255 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Department of Anatomy and Cell Biology, the Carver College of Medicine, University of Iowa Holden Comprehensive Cancer Center, University of Iowa T32GM007337 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) School of Dentistry, University of Iowa R01CA200673 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 12/01/2019
- Academic Unit
- Dermatology; Microbiology and Immunology; Anatomy and Cell Biology; Endodontics; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284326202771
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