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| Status |
Public on Dec 16, 2017 |
| Title |
Snail-dependent epithelial splicing regulatory protein 1 (ESRP1) silencing drives malignant transformation of human pulmonary epithelial cells [miRNA] |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus; Human alphaherpesvirus 1; Human betaherpesvirus 5; Murid betaherpesvirus 1; human gammaherpesvirus 4; JC polyomavirus; Human immunodeficiency virus 1; Murid gammaherpesvirus 4; Human gammaherpesvirus 8; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
The significance of epithelial-to-mesenchymal transition (EMT)-inducing transcription factors in the onset of non-small cell lung cancer has not been resolved. Here, we report increased Snail expression in pulmonary premalignant lesions relative to histologically normal-appearing pulmonary epithelium. Utilizing immortalized human pulmonary epithelial cells and isogenic derivatives, we document Snail-dependent anchorage-independent growth of the epithelial cells in vitro, as well as transformation, primary tumor growth, and metastatic behavior in vivo. Epithelial splicing regulatory protein 1 (ESRP1) tumor suppressor silencing was a requirement for Snail-driven transformation in vivo, and we identified ESRP1 loss in Snail-expressing pulmonary premalignant lesions in situ. Snail drives these and other carcinogenic signaling programs in an ALDH+CD44+CD24- pulmonary stem cell subset in which ESRP1 and stemness-repressing micro-RNAs are inhibited.
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| Overall design |
Two distinct HBEC cell lines were transduced with a retroviral vector containing human SNAI1 (Snail) cDNA or the empty vector. Their micro RNAs were profiled to determine the impact of ectopic Snail expression on the isogenic epithelial background of the HBECs.
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| Contributor(s) |
Walser TC, Jing Z, Tran LM, Lin Y, Yakobian N, Wang G, Krysan K, Zhu LX, Sharma S, Lee M, Belperio JA, Ooi A, Gomperts BN, Shay JW, Larsen JE, Minna JD, Hong L, Fishbein MC, Dubinett SM |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Dec 15, 2017 |
| Last update date |
Jan 24, 2018 |
| Contact name |
Linh My Tran |
| E-mail(s) |
linhtran@ucla.edu
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| Organization name |
University of Los Angeles
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| Department |
Medicine - Pulmonary & Critical Care
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| Lab |
Dubinett Lab
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| Street address |
Box 951690, 37-131 CHS
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095-1690 |
| Country |
USA |
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| Platforms (1) |
| GPL7723 |
miRCURY LNA microRNA Array, v.11.0 - hsa, mmu & rno |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE108137 |
Snail-dependent epithelial splicing regulatory protein 1 (ESRP1) silencing drives malignant transformation of human pulmonary epithelial cells |
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| Relations |
| BioProject |
PRJNA422652 |
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