Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb

Respiratory Research
Jean-Bosco TagneMaria I Ramirez

Abstract

The transcription factor NK2 homeobox 1 (Nkx2-1) plays essential roles in epithelial cell proliferation and differentiation in mouse and human lung development and tumorigenesis. A better understanding of genes and pathways downstream of Nkx2-1 will clarify the multiple roles of this critical lung factor. Nkx2-1 regulates directly or indirectly numerous protein-coding genes; however, there is a paucity of information about Nkx2-1-regulated microRNAs (miRNAs). By miRNA array analyses of mouse epithelial cell lines in which endogenous Nkx2-1 was knocked-down, we revealed that 29 miRNAs were negatively regulated including miR-200c, and 39 miRNAs were positively regulated by Nkx2-1 including miR-1195. Mouse lungs lacking functional phosphorylated Nkx2-1 showed increased expression of miR-200c and alterations in the expression of other top regulated miRNAs. Moreover, chromatin immunoprecipitation assays showed binding of NKX2-1 protein to regulatory regions of these miRNAs. Promoter reporter assays indicated that 1kb of the miR-200c 5' flanking region was transcriptionally active but did not mediate Nkx2-1- repression of miR-200c expression. 3'UTR reporter assays support a direct regulation of the predicted targets Nfib and Myb by m...Continue Reading

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Citations

May 25, 2016·Molecular and Cellular Pediatrics·Claudio Nardiello, Rory E Morty
Jul 26, 2019·Expert Review of Respiratory Medicine·Patrick A Philpot, Vineet Bhandari
Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty
Mar 19, 2019·Oncology Letters·Weiyun WuJuanhua Quan

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Datasets Mentioned

BETA
GSE47055

Methods Mentioned

BETA
Assay
immunoprecipitation
ChIP
transfections
PCR
transfection
ChIP-chip

Software Mentioned

miRNA QC Tool
GATHER ( Gene Annotation Tool to Help Explain Relationships )
TargetScanMouse
Affymetrix Expression Console
UCSC Mouse Genome Browser

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