Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma

Mortoglou, M., Djordjevic, A.B., Djordjevic, V., Collins, H., York, L., Mani, K., Valle, E., Wallace, D. and Uysal Onganer, P. 2021. Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma. Archives of Toxicology. 96, p. 467–485. https://doi.org/10.1007/s00204-021-03196-9

TitleRole of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma
TypeJournal article
AuthorsMortoglou, M., Djordjevic, A.B., Djordjevic, V., Collins, H., York, L., Mani, K., Valle, E., Wallace, D. and Uysal Onganer, P.
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal and aggressive malignancies with a 5-year survival rate less than 9%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. Alterations of miR expressions can lead to apoptosis, angiogenesis, and metastasis.
The role of environmental pollutants such as cadmium (Cd) in PDAC has been suggested but not fully understood. This study underlines the role of miRs (miR-221, miR-155, miR-126) in response to cadmium chloride (CdCl2) in vitro. Lethal concentration (LC50) values for CdCl2 resulted in a toxicity series of AsPC-1>HPNE>BxPC3>Panc-1=Panc-10.5. Following the treatment with CdCl2, miR-221 and miR-155 were significantly overexpressed, whereas miR-126 was downregulated.
An increase in epithelial–mesenchymal transition (EMT) via the dysregulation of mesenchymal markers such as Wnt-11,E-cadherin, Snail, and Zeb1 was also observed. Hence, this study has provided evidence to suggest that the environmental pollutant Cd can have a signifcant role in the development of PDAC, suggesting a signifcant correlation between miRs and Cd exposure during PDAC progression. Further studies are needed to investigate the precise role of miRs in PDAC progression as well as the role of Cd and other environmental pollutants.

JournalArchives of Toxicology
Journal citation96, p. 467–485
ISSN1432-0738
0340-5761
Year2021
PublisherSpringer
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1007/s00204-021-03196-9
Publication dates
Published online14 Dec 2021
Published in print2022

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