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| Status |
Public on Dec 22, 2015 |
| Title |
The homeobox transcription factor Nkx2-1 regulates microRNAs controlling downstream gene silencing in lung epithelial cells (microRNA) |
| Platform organism |
synthetic construct |
| Sample organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Cell-specific gene expression is achieved by a combination of mechanisms including transcriptional and post-transcriptional regulation. The transcription factor Nkx2-1, essential for lung cell differentiation, mainly acts in transcriptional activation but can directly or indirectly repress gene expression. microRNAs are a class of small non-coding RNA that control one of the major mechanisms of gene repression. To identify miRNAs regulated by Nkx2-1 that may mediate its repressing effects, we knocked-down Nkx2-1 in mouse lung epithelial cell lines and systematically identified targets by genome-wide miR and mRNA expression analyses. Nkx2-1 controls expression of miRs known to contribute to lung cell differentiation in development and disease and others not previously described. Amongst the significantly altered miRs, the mir-106a-363 cluster, miR-1195, miR-378, and miR-346 are directly correlated with the levels of Nkx2-1, whereas miR-200c/b, miR-221, and miR- 222 are inversely correlated. These miRNAs are expressed in embryonic lung at day E11.5, and/or E19.5 determined by in-situ hybridization. Expression of predicted targets of mir-1195, mir-346 and miR-200c and mir-221/222 were evaluated by mRNA expression microarrays in Nkx2-1 knockdown cells identifying those anti-correlated to the corresponding miRNA expression. Genes regulated by mir-1195, Cyp2s1 and Map3k2, by mir-346, Klf6, and miR-200c, Myb, Nfib, and Six1, were validated by qRT-PCR. Inhibition of mir-1195 confirms the inverse correlation of this miRNA with its putative targets Cyp2s1 and Map3k2. This miRNA-mRNA expression analysis identifies potential paths of Nkx2-1 mediated gene repression, and contributes to the understanding of gene regulation in lung epithelial differentiation and development.
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| Overall design |
Nkx2-1 mRNA was knocked down in lung epithelial cells using a lentivirus expressing a shRNA targeting Nkx2-1 (n=3) and compared to empty vector controls (n=3).
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| Contributor(s) |
Tagne J, Mohtar OR, Campbell JD, Lakshminarayanan M, Huang J, Hinds A, Lu J, Ramirez MI |
| Citation(s) |
25763778 |
| Submission date |
May 17, 2013 |
| Last update date |
May 02, 2017 |
| Contact name |
Joshua David Campbell |
| E-mail(s) |
camp@bu.edu
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| Organization name |
Boston University
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| Street address |
72 East Concord St.
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL8786 |
[miRNA-1] Affymetrix Multispecies miRNA-1 Array |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE47055 |
The homeobox transcription factor Nkx2-1 regulates microRNAs controlling downstream gene silencing in lung epithelial cells |
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| Relations |
| BioProject |
PRJNA203383 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47053_RAW.tar |
850.0 Kb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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