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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 |
Liver carcinoma cell line Huh7 samples were transfected with each siRNA (siCtrl #2 scramble, #3 scramble, siELIT-1 #2, or siELIT-1 #3). At 24 h after the first transfection, cells were transfected with these siRNAs, again. At 6 h after the second transfection, cells were treated with or without 10 ng/mL TGF-b for 48 h. Total RNA was isolated from cultured cells using RNeasy Mini Kit and followed by microarray analysis.
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| Contributor(s) |
Sakai S, Ohhata T, Kitagawa M |
| Citation(s) |
30952633 |
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| Submission date |
Mar 28, 2019 |
| Last update date |
Apr 13, 2019 |
| Contact name |
Satoshi Sakai |
| E-mail(s) |
[email protected]
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| Organization name |
Hamamatsu University School of Medicine
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| Department |
Virology and Parasitology
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| Street address |
1-20-1 Handayama, Higashi-ku
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| 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 |
PRJNA529685 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE129008_RAW.tar |
61.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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