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| Status |
Public on Mar 28, 2017 |
| Title |
A Long Noncoding RNA TTN-AS1 Controls Esophageal Squamous Cell Carcinomas by Functioning as a Competing Endogenous RNA and Scaffolding mRNA Stabilizing Protein HuR [Affymetrix] |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
BACKGROUND & AIMS: Emerging long non-coding RNAs (lncRNAs) have been demonstrated to be associated with progression of various cancers. In the current study, we identified a novel lncRNA-TTN-AS1 and dissected the underlying mechanisms by which lncRNA-TTN-AS1 induced carcinogenesis of esophageal squamous cell carcinoma (ESCC).
METHODS: ESCC and adjacent non-malignant specimens from 7 ESCC patients were chosen to analyze the expression profiles of lncRNA-miRNA-mRNA using multiple microarrays. The novel lncRNA-TTN-AS1 was identified using multiple bioinformatics platforms. Levels of lncRNA-TTN-AS1 in tissues from 148 ESCC patients were verified by qRT-PCR and in situ hybridization. The biological function and mechanism of action of lncRNA-TTN-AS1 were performed both in vivo and in vitro using gain-of and loss-of function assays on TE-13 cells and KYSE-410 cells, luciferase reporter assays, RNA immunoprecipitation (RIP) assays and RNA pull-down assays.
RESULTS: lncRNA-TTN-AS1 levels were upregulated in ESCC tissues compared with adjacent non-malignant tissues, and correlated with poor prognosis. LncRNA-TTN-AS1, as an oncogene, promoted ESCC cell proliferation and prevented apoptosis. Additionally, lncRNA-TTN-AS1 increased snail1 levels by competitively binding to miR-133b, thereby facilitating epithelial-mesenchymal transition (EMT) cascades. Sharing miR-133b binding sites, lncRNA-TTN-AS1 as a ceRNA also derepressed FSCN1 mediated by miR-133b. Notably, lncRNA-TTN-AS1 stabilized FSCN1 mRNA by interacting directly with the mRNA stabilizing protein HuR, resulting in ESCC invasion-cascades and activation of FSCN1/β-catenin.
CONCLUSION: lncRNA-TTN-AS1 sponges miR-133b to govern the expression of snial1 and FSCN1, which promotes ESCC cell proliferation and metastasis. It also combines with HuR to modulate FSCN1 in ESCC cell lines. Our findings may provide a novel target for ESCC anti-metastatic therapies.
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| Overall design |
Using microarrays to compare expression profiles of miRNAs in ESCC tissues and adjacent normal tissues.
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| Contributor(s) |
Lin C, Zhang S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Mar 27, 2017 |
| Last update date |
May 03, 2017 |
| Contact name |
chenyu lin |
| E-mail(s) |
[email protected]
|
| Phone |
08615105603949
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| Organization name |
China Pharmaceutical University
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| Department |
Life science
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| Lab |
Hanmei Xu
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| Street address |
Longmian Road No.639
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| City |
Nanjing |
| ZIP/Postal code |
211100 |
| Country |
China |
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| Platforms (1) |
| GPL21572 |
[miRNA-4] Affymetrix Multispecies miRNA-4 Array [ProbeSet ID version] |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE97051 |
lncRNA-miRNA-mRNA expression profiles in esophageal squamous carcinoma tissues and adjacent normal tissues |
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| Relations |
| BioProject |
PRJNA380703 |
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