Lost miR-141 and upregulated TM4SF1 expressions associate with poor prognosis of pancreatic cancer: regulation of EMT and angiogenesis by miR-141 and TM4SF1 via AKT.
Cancer Biol Ther
; 21(4): 354-363, 2020 04 02.
Article
em En
| MEDLINE
| ID: mdl-31906774
ABSTRACT
Background:
Transmembrane-4-L-six-family-1 (TM4SF1) functions to regulate cell growth and mobility and TM4SF1 expression was upregulated in pancreatic cancer. This study further investigated the role of TM4SF1 in regulating pancreatic cancer epithelial-mesenchymal transition (EMT) and angiogenesis and the underlying molecular events.Methods:
Tissue specimens were collected from 90 pancreatic cancer patients for immunohistochemical and qRT-PCR analysis of miR-141 and TM4SF1 levels, respectively. Pancreatic cancer cell lines were used for in vitro assays, while nude mice were used for the in vivo assay.Results:
TM4SF1 expression was upregulated, whereas miR-141 expression was lost in pancreatic cancer tissues, both of which was associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Furthermore, miR-141 was able to target and reduce TM4SF1 expression in pancreatic cancer cells and miR-141 expression inhibited pancreatic cancer cell EMT in vitro and Matrigel plug angiogenesis and lung metastasis in nude mice. At the gene level, miR-141 directly targeted and reduced TM4SF1 expression and in turn induced E-cadherin expression and reduced VEGF-A expression by suppressing activation of the AKT signaling pathway.Conclusions:
This study demonstrated that upregulated TM4SF1 and lost miR-141 expression were associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Lost miR-141 expression but induced TM4SF1 expression altered expression of VEGF-A and E-cadherin and promoted pancreatic cancer cell EMT and angiogenesis via the AKT signaling pathway, suggesting that targeting of miR-141 and TM4SF1 may be a potential therapeutic strategy to control pancreatic cancer.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Regulação Neoplásica da Expressão Gênica
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MicroRNAs
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Transição Epitelial-Mesenquimal
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Neoplasias Pulmonares
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Proteínas de Neoplasias
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Antígenos de Superfície
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Neovascularização Patológica
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article