Long noncoding RNA XIST regulates the EGF receptor to promote TGF-ß1-induced epithelial-mesenchymal transition in pancreatic cancer.
Biochem Cell Biol
; 98(2): 267-276, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31013436
ABSTRACT
BACKGROUND:
This study focuses on the lncRNA XIST (X inactive-specific transcript), an lncRNA involved in multiple human cancers, and investigates the functional significance of XIST and the molecular mechanisms underlying the epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC).METHODS:
Clinical specimens from 25 patients as well as 5 human PC cell lines were analyzed for XIST, YAP, and microRNA(miR)-34a by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. To investigate how XIST influences cell proliferation, invasiveness, and apoptosis in PC, we performed the CCK-8 assays, Transwell assays, and flow cytometry. Luciferase reporter assays, qRT-PCR, and Western blot were applied to prove that miR-34a directly binds to XIST.RESULTS:
Up-regulation of XIST and Yes associated protein (YAP) and down-regulation of miR-34a were consistently observed in the clinical specimens and PC cell lines. Silencing XIST reduced the expression of YAP and suppressed transforming growth factor (TGF)-ß1-induced EMT, while over-expression of XIST increased the expression of YAP and promoted EMT. In addition, inhibition of epidermal growth factor receptor (EGFR) hampered the XIST-promoted EMT. The results from the luciferase reporter assays confirmed that miR-34a directly targets XIST and suggested that XIST regulates cell proliferation, invasiveness, and apoptosis in PC by sponging miR-34a.CONCLUSIONS:
XIST promotes TGF-ß1-induced EMT by regulating the miR-34a-YAP-EGFR axis in PC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Regulação Neoplásica da Expressão Gênica
/
Fator de Crescimento Transformador beta1
/
Transição Epitelial-Mesenquimal
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article