Deregulated expression of miR-107 inhibits metastasis of PDAC through inhibition PI3K/Akt signaling via caveolin-1 and PTEN.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) displays a highly aggressive malignancy and is considered to be an incurable and rapidly lethal disease. MicroRNAs (miRNAs) are small non-coding RNAs of approximately nucleotides that regulate several aspects of tumors pathogenesis, including migration, invasion, metastasis and epithelial-mesenchymal transition. We have found that miR-107 was significantly high expression in PDAC tissues and cells. High miR-107 expression is associated with poor clinicopathological parameters and prognosis in PDAC patients. Deregulated expression of miR-107 in PDAC cells (AsPC-1 and Panc-1) is sufficient to reduce cell migration and invasion, and to induce upregulation of epithelial markers (β-catenin, ZO-1 and E-cadherin) and a decrease of mesenchymal marker expression (ZEB-1 and vimentin). We also found that the caveolin-1, PTEN and p-Akt expression are modulated by miR-107 in PDAC cells. Moreover, our study clearly demonstrated that deregulated expression of miR-107 inhibited cell migration and invasion and EMT by up-regulation of caveolin-1 and PTEN, and inhibition of PI3K/Akt signaling in PDAC cells. Our study suggested that miR‑107 expression might both be a useful indicator of the metastatic potential and provided a new potential therapeutic target in PDAC.

• Authors: Junjie Xiong, Dan Wang, Ailin Wei, Huimin Lu, Chunlu Tan, Ang Li, Jie Tang, Yichao Wang, Sirong He, Xubao Liu, Weiming Hu
• Journal: Experimental cell research (Exp Cell Res) Vol. 361 Issue 2 Pg. 316-323 (12 15 2017) ISSN: 1090-2422 [Electronic] United States
• PMID: 29111166 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• CAV1 protein, human
• CDH1 protein, human
• CTNNB1 protein, human
• Cadherins
• Caveolin 1
• MIRN107 microRNA, human
• MicroRNAs
• TJP1 protein, human
• Vimentin
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• Zonula Occludens-1 Protein
• beta Catenin
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Aged
• Antigens, CD
• Cadherins (genetics, metabolism)
• Carcinoma, Pancreatic Ductal (diagnosis, genetics, metabolism, pathology)
• Caveolin 1 (genetics, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• PTEN Phosphohydrolase (genetics, metabolism)
• Pancreatic Neoplasms (diagnosis, genetics, metabolism, pathology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction
• Vimentin (genetics, metabolism)
• Zinc Finger E-box-Binding Homeobox 1 (genetics, metabolism)
• Zonula Occludens-1 Protein (genetics, metabolism)
• beta Catenin (genetics, metabolism)