The inhibitory effect of LINC00261 upregulation on the pancreatic cancer EMT process is mediated by KLF13 via the mTOR signaling pathway
Clin. transl. oncol. (Print)
; 24(6): 1059-1072, junio 2022.
Article
em En
| IBECS
| ID: ibc-203806
Biblioteca responsável:
ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
PurposeThe long noncoding RNA LINC00261 was reported to be involved in carcinogenesis and has been validated as a tumor suppressor in pancreatic cancer (PC); however, how LINC00261 is regulated has not been fully examined. Here, we attempted to investigate the upstream and downstream targets of LINC00261 in PC.MethodsLINC00261 expression in PC tissues was examined by the Gene Expression Omnibus (GEO) datasets and the Gene Expression Profiling Interactive Analysis (GEPIA) database. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were performed to detect the expression level of LINC00261 in PC cells. The location of LINC00261 in PC cells was identified by RNA fluorescence in situ hybridization (RNA-FISH). Cell Counting Kit-8 (CCK-8), cell apoptosis assay, transwell invasion and migration assays testified the critical role of LINC00261 in PC. The luciferase reporter assay was applied to confirm the binding of LINC00261 to its upstream transcription factor KLF13. The changes in LINC00261 related target protein levels were analyzed by Western blotting assay.ResultsLINC00261 was significantly lower in PC tissues and was mainly concentrated in the nucleus. Overexpression of LINC00261 inhibited the invasion and migration of PC cells. Mechanistically, transcription factor KLF13 was confirmed to inhibit the epithelial-mesenchymal transition (EMT) process of PC cells by promoting the transcription of LINC00261 and suppressing the expression of metastasis-associated proteins, such as matrix metalloproteinase MMP2 and vimentin, thus inhibiting the metastasis of PC.ConclusionLINC00261 regulates PC cell metastasis through the KLF13-LINC00261-mTOR-P70S6K1-S6 signaling pathway, which provides a significant set of potential PC therapeutic targets.
Palavras-chave
Texto completo:
1
Coleções:
06-national
/
ES
Base de dados:
IBECS
Assunto principal:
Fatores de Transcrição
/
Movimento Celular
/
Proteínas de Ciclo Celular
/
MicroRNAs
/
Linhagem Celular Tumoral
/
Proliferação de Células
/
Fatores de Transcrição Kruppel-Like
/
Transição Epitelial-Mesenquimal
Limite:
Humans
Idioma:
En
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2022
Tipo de documento:
Article