TY - JOUR
T1 - Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma
AU - Mortoglou, Maria
AU - Buha Djordjevic, Aleksandra
AU - Djordjevic, Vladimir
AU - Collins, Hunter
AU - York, Lauren
AU - Mani, Katherine
AU - Valle, Elizabeth
AU - Wallace, David
AU - Uysal-Onganer, Pinar
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cadmium
KW - EMT
KW - LC50
KW - microRNAs
KW - Non-coding RNAs
KW - Pancreatic ductal adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=85121308426&partnerID=8YFLogxK
U2 - 10.1007/s00204-021-03196-9
DO - 10.1007/s00204-021-03196-9
M3 - Article
C2 - 34905088
AN - SCOPUS:85121308426
SN - 0340-5761
VL - 96
SP - 467
EP - 485
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 2
ER -