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| Status |
Public on Apr 12, 2019 |
| Title |
Long noncoding RNA ELIT-1 acts as a Smad3 cofactor to facilitate TGF-β/Smad signaling and promote epithelial-mesenchymal transition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
TGF-β is involved in various biological processes, including development, differentiation, growth regulation, and epithelial-mesenchymal transition (EMT). In TGF-β/Smad signaling, receptor-activated Smad complexes activate or repress their target gene promoters. Smad cofactors are a group of Smad-binding proteins that promote recruitment of Smad complexes to these promoters. Long noncoding RNAs (lncRNAs), that behave as Smad cofactors have thus far not been identified. Here, we characterize a novel lncRNA EMT-associated lncRNA induced by TGF-β-1(ELIT-1). ELIT-1 was induced by TGF-β-stimulation via the TGF-β/Smad pathway in TGF-β-responsive cell lines. ELIT-1-depletion abrogated TGF-β-mediated EMT progression and expression of TGF-β target genes including Snail, a transcription factor critical for EMT. A positive correlation between high expression of ELIT-1 and poor prognosis in lung adenocarcinoma and gastric cancer patients suggests that ELIT-1 may be useful as a prognostic and therapeutic target. RIP assays revealed that ELIT-1 bound to Smad3, but not Smad2. In conjunction with Smad3, ELIT-1 enhanced Smad-responsive promoter activities by recruiting Smad3 to the promoters of its target genes including Snail, other TGF-β-target genes, and ELIT-1 itself. Collectively, these data show that ELIT-1 is a novel trans-acting lncRNA that forms a positive feedback loop to enhance TGF-β/Smad3 signaling and promote EMT progression.
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| Overall design |
To identify the genes induced by HBV replication, HBV genome containing episomal vectors (Ae, Bj35, Bj56) or its empty vector (pEB) were transfected in liver carcinoma cell line Huh7. After puromycin screening, the transfectants were subjected to purify its total RNA and followed by microarray analysis.
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| Contributor(s) |
Ohhata T, Sakai S, Kitagawa M |
| Citation(s) |
30952633 |
| |
| Submission date |
Mar 28, 2019 |
| Last update date |
Apr 13, 2019 |
| Contact name |
Tatsuya Ohhata |
| E-mail(s) |
ohhata@hama-med.ac.jp
|
| Organization name |
Hamamatsu University School of Medicine
|
| Department |
Department of Molecular Biology
|
| Street address |
Higashi-ku Handayama 1-20-1
|
| City |
Hamamatsu |
| State/province |
Shizuoka |
| ZIP/Postal code |
431-3192 |
| Country |
Japan |
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| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA529580 |
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