MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1

Ji Qi, Shawn J. Rice, Anna C. Salzberg, E. Aaron Runkle, Jason Liao, Dani S. Zander, David Mu

Research output: Contribution to journalArticle

62 Scopus citations

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 β (TGFβ) 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.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalCell Cycle
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Qi, J., Rice, S. J., Salzberg, A. C., Runkle, E. A., Liao, J., Zander, D. S., & Mu, D. (2012). MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1. Cell Cycle, 11(1), 177-186. https://doi.org/10.4161/cc.11.1.18576