Genome-Wide Analysis of the FOXA1 Transcriptional Network Identifies Novel Protein-Coding and Long Noncoding RNA Targets in Colorectal Cancer Cells

Author:

Lazar Sarah B.1,Pongor Lorinc2,Li Xiao Ling1,Grammatikakis Ioannis1,Muys Bruna R.1,Dangelmaier Emily A.1,Redon Christophe E.2,Jang Sang-Min2,Walker Robert L.3,Tang Wei4,Ambs Stefan4,Harris Curtis C.5,Meltzer Paul S.3,Aladjem Mirit I.2,Lal Ashish1ORCID

Affiliation:

1. Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA

2. Developmental Therapeutics Branch, Laboratory of Molecular Pharmacology, CCR, NCI, NIH, Bethesda, Maryland, USA

3. Molecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, Maryland, USA

4. Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, Maryland, USA

5. Molecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, Maryland, USA

Abstract

Differentiation status of tumors is correlated with metastatic potential and malignancy. FOXA1 (forkhead box A1) is a transcription factor known to regulate differentiation in certain tissues. Here, we investigate FOXA1 function in human colorectal cancer (CRC). We found that FOXA1 is robustly expressed in the normal human colon but significantly downregulated in colon adenocarcinoma. Applying FOXA1 chromatin immunoprecipitation coupled with deep sequencing and transcriptome analysis upon FOXA1 knockdown in well-differentiated CRC cells and FOXA1 overexpression in poorly differentiated CRC cells, we identified novel protein-coding and lncRNA genes regulated by FOXA1.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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