Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma
| Autor: | Duowu Zou, Jun Liu, Yaozong Yuan, Weiyi Wang, Yunwei Sun, Qiwen Ben |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Nicotine
Epithelial-Mesenchymal Transition endocrine system diseases Cell Survival Endocrinology Diabetes and Metabolism Mice Nude In situ hybridization miR-155 Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor microRNA medicine Animals Humans Epithelial–mesenchymal transition Gene knockdown Hepatology business.industry Gastroenterology Membrane Proteins Neoplasms Experimental digestive system diseases Gene Expression Regulation Neoplastic Pancreatic Neoplasms MicroRNAs Tumor progression Cell culture 030220 oncology & carcinogenesis Cancer research 030211 gastroenterology & hepatology Carrier Proteins business Carcinoma Pancreatic Ductal medicine.drug |
| Zdroj: | Pancreatology. 20:698-708 |
| ISSN: | 1424-3903 |
| DOI: | 10.1016/j.pan.2020.04.004 |
| Popis: | Background Nicotine, the major component of cigarette smoke, has been reported to promote pancreatic ductal adenocarcinoma (PDAC) growth and invasion. Deregulation of microRNA (miRNA) expression is found in many cancers, including PDAC. The effects of nicotine on miRNAs change in PDAC progression remain unknown. Methods The effects of cigarette smoking/nicotine exposure on PDAC cell lines and tissues were evaluated. Quantitative real-time PCR and in situ hybridization assays were used to determine miR-155-5p expression in human PDAC tissue and cell lines upon cigarette smoking/nicotine exposure. Bioinformatics, loss-of-function experiments, luciferase reporter assay were performed to validate Nedd4 family interacting protein 1 (NDFIP1) as a direct target of miR-155-5p. The potentials of systemic miR-155-5p inhibitor-based therapy in overcoming nicotine exposure were evaluated in tumor xenograft model. Results Nicotine promoted PDAC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a dose-response manner. MiR-155-5p was found to be highly expressed in PDAC cell lines and tissues upon cigarette smoking/nicotine exposure. Functional studies showed that miR-155-5p knockdown could override the enhancement of oncogenic activity due to nicotine exposure in vitro and in vivo by directly interacting with the 3′ untranslated regions (UTRs) of NDFIP1. Conclusions These data demonstrate that nicotine-regulated miR-155-5p/NDFIP1 promotes tumor progression and EMT of PDAC. |
| Databáze: | OpenAIRE |
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