Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs
Аутори
Mortoglou, MariaManić, Luka
Buha-Đorđević, Aleksandra
Bulat, Zorica
Đorđević, Vladimir
Manis, Katherine
York, Lauren
Valle, Elizabeth
Wallace, David
Uysal-Onganer, Pinar
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increas...ing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis.
Кључне речи:
apoptosis / environmental toxins / microRNAs / nickel / non-coding RNAs / pancreatic ductal adenocarcinomaИзвор:
Toxics, 2022, 10, 3Издавач:
- MDPI
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
- Oklahoma State University Center for Health Sciences (OVPR) Pilot/Seed Grant (AG154391) and Presidential Fellowship (to KM, LY, and LV) D.R.W.;
- University of Westminster, School of Life Sciences Research Enhancement Grant 2020 P.U.-O., M.M. is supported by University of Westminster SLS PhD Studentship
DOI: 10.3390/toxics10030148
ISSN: 2305-6304
WoS: 000774451400001
Scopus: 2-s2.0-85127707622
Институција/група
PharmacyTY - JOUR AU - Mortoglou, Maria AU - Manić, Luka AU - Buha-Đorđević, Aleksandra AU - Bulat, Zorica AU - Đorđević, Vladimir AU - Manis, Katherine AU - York, Lauren AU - Valle, Elizabeth AU - Wallace, David AU - Uysal-Onganer, Pinar PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4352 AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis. PB - MDPI T2 - Toxics T1 - Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs VL - 10 IS - 3 DO - 10.3390/toxics10030148 ER -
@article{ author = "Mortoglou, Maria and Manić, Luka and Buha-Đorđević, Aleksandra and Bulat, Zorica and Đorđević, Vladimir and Manis, Katherine and York, Lauren and Valle, Elizabeth and Wallace, David and Uysal-Onganer, Pinar", year = "2022", abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis.", publisher = "MDPI", journal = "Toxics", title = "Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs", volume = "10", number = "3", doi = "10.3390/toxics10030148" }
Mortoglou, M., Manić, L., Buha-Đorđević, A., Bulat, Z., Đorđević, V., Manis, K., York, L., Valle, E., Wallace, D.,& Uysal-Onganer, P.. (2022). Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs. in Toxics MDPI., 10(3). https://doi.org/10.3390/toxics10030148
Mortoglou M, Manić L, Buha-Đorđević A, Bulat Z, Đorđević V, Manis K, York L, Valle E, Wallace D, Uysal-Onganer P. Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs. in Toxics. 2022;10(3). doi:10.3390/toxics10030148 .
Mortoglou, Maria, Manić, Luka, Buha-Đorđević, Aleksandra, Bulat, Zorica, Đorđević, Vladimir, Manis, Katherine, York, Lauren, Valle, Elizabeth, Wallace, David, Uysal-Onganer, Pinar, "Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs" in Toxics, 10, no. 3 (2022), https://doi.org/10.3390/toxics10030148 . .