Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma

Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:20

Enthalten in:

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al. - 20(2020), 4 vom: 10. Juni, Seite 698-708

Sprache:

Englisch

Beteiligte Personen:

Ben, Qiwen [VerfasserIn]
Sun, Yunwei [VerfasserIn]
Liu, Jun [VerfasserIn]
Wang, Weiyi [VerfasserIn]
Zou, Duowu [VerfasserIn]
Yuan, Yaozong [VerfasserIn]

Links:

Volltext

Themen:

6M3C89ZY6R
Carrier Proteins
Journal Article
MIRN155 microRNA, human
Membrane Proteins
MiR-155-5p
MicroRNAs
NDFIP1
NDFIP1 protein, human
Nicotine
Pancreatic ductal adenocarcinoma

Anmerkungen:

Date Completed 09.04.2021

Date Revised 09.04.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.pan.2020.04.004

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM309383358