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The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer.
Ma, Lixin; Zhai, Bo; Zhu, Huaqiang; Li, Weidong; Jiang, Wenjing; Lei, Liwang; Zhang, Shujun; Qiao, Haiquan; Jiang, Xian; Sun, Xueying.
Afiliação
  • Ma L; 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Zhai B; 2Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Zhu H; 3The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Li W; 4Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Jinan, 250021 China.
  • Jiang W; 2Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Lei L; 3The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Zhang S; 3The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Qiao H; 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Jiang X; 5Department of Pathology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
  • Sun X; 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 China.
Cancer Cell Int ; 19: 248, 2019.
Article em En | MEDLINE | ID: mdl-31572065
BACKGROUND: Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear. METHODS: Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial-mesenchymal transition (EMT) by co-interacting the TGF-ß pathway was examined. RESULTS: In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-ß pathway stimulated by TGF-ß ligand. CONCLUSIONS: The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article