MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1
- 1 January 2012
- journal article
- Published by Informa UK Limited in Cell Cycle
- Vol. 11 (1), 177-186
- https://doi.org/10.4161/cc.11.1.18576
Abstract
Thyroid transcription factor 1 (TTF-1 or NKX2-1) is an essential fetal lung developmental factor, which can be recurrently activated by gene amplification in adult lung cancer. We have discovered the first microRNA (i.e., miR-365) that directly regulates TTF-1 by interacting with its 3’-untranslated region. By gene expression profiling, we identified other putative targets of miR-365 and miR-365*. In line with the microRNA/target relationship, the expression patterns of miR-365 and TTF-1 were in an inverse relationship in human lung cancer. Exploration of human lung cancer genomics data uncovered that TTF-1 gene amplification was significantly associated with DNA copy number loss at one of the two genomic loci encoding the precursor RNA of mature miR-365 (i.e., mir-365-1). This implies the existence of genetic selection pressure to lose the repressive miR-365 that would otherwise suppress amplified TTF-1. We detected a signaling loop between transforming growth factor beta (TGFb) and miR-365 and this loop reinforced suppression of TTF-1 via miR-365. Mir-365 also targeted an epithelial mesenchymal transition (EMT)-promoting gene HMGA2. In summary, these data connect the lung transcriptional program to the microRNA network.Keywords
This publication has 50 references indexed in Scilit:
- Suppression of lung adenocarcinoma progression by Nkx2-1Nature, 2011
- Causes and consequences of microRNA dysregulation in cancerNature Reviews Genetics, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancerOncogene, 2008
- Characterizing the cancer genome in lung adenocarcinomaNature, 2007
- MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed PairingMolecular Cell, 2007
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006
- Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA TargetsCell, 2005
- The functions of animal microRNAsNature, 2004
- MicroRNAs: small RNAs with a big role in gene regulationNature Reviews Genetics, 2004