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

Maria Mortoglou, Aleksandra Buha Djordjevic, Vladimir Djordjevic, Hunter Collins, Lauren York, Katherine Mani, Elizabeth Valle, David Wallace, Pinar Uysal-Onganer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 > BxPC-3 > 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 significant role in the development of PDAC, suggesting a significant 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.

Original languageEnglish
Pages (from-to)467-485
Number of pages19
JournalArchives of Toxicology
Volume96
Issue number2
DOIs
StatePublished - Feb 2022

Keywords

  • Apoptosis
  • Cadmium
  • EMT
  • LC50
  • microRNAs
  • Non-coding RNAs
  • Pancreatic ductal adenocarcinoma

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