Functional Role of A Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis
Menée in vitro et in vivo sur des modèles de carcinome épidermoïde de l'œsophage, cette étude met en évidence des mécanismes par lesquels un long ARN non codant (TTN-AS1) favorise la prolifération des cellules cancéreuses et le processus métastatique
Résumé en anglais
Purpose: Emerging studies demonstrate that long non-coding RNAs (lncRNAs)participate in the regulation of various cancers. In the current study, a novel lncRNA-TTN-AS1 has been identified and explored in esophageal squamous cell carcinoma (ESCC).
Experimental Design: To discover a new regulatory circuitry in which RNAs crosstalk with each other, the transcriptome of lncRNA-miRNA-mRNA from ESCC and adjacent non-malignant specimens were analyzed using multiple microarrays and diverse bioinformatics platforms. The functional role and mechanism of a novel lncRNA-TTN-AS1 were further investigated by gain-of and loss-off function assays in vivo and in vitro. An ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b and FSCN1, was validated by qRT-RCP and in situ hybridization using samples from 148 patients.
Results: LncRNA-TN-AS1 as an oncogene, is highly expressed in ESCC tissues and cell lines, and promotes ESCC cell proliferation and metastasis. Mechanistically, lncRNA-TTN-AS1 promotes expression of transcription factor Snail1 by competitively binding miR-133b, resulting in the epithelial-mesenchymal transition (EMT) cascade. Moreover, lncRNA-TTN-AS1 also induces FSCN1 expression by sponging miR-133b and upregulation of mRNA stabilizing protein HuR, which further promotes ESCC invasion cascades. We also discovered and validated a clinically applicable ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b and FSCN1, that is significantly associated with overall survival and provides additional prognostic evidence for ESCC patients.
Conclusions: As a novel regulator, lncRNA-TTN-AS1 plays an important role in ESCC cell proliferation and metastasis. The lncRNA-TTN-AS1/miR133b/FSCN1 regulatory axis provides bona fide targets for anti-ESCC therapies.
