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

Mortoglou, Maria; Djordjević, Aleksandra Buha; Djordjević, Vladimir; Collins, Hunter; York, Lauren; Mani, Katherine; Valle, Elizabeth Ranier Martins do; Wallace, David R.; Uysal-Onganer, Pinar

doi:10.1007/s00204-021-03196-9

Cited by 11 publications

(17 citation statements)

References 143 publications

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“…Each of the five cell lines was plated as it has been previously described [ 60 ]. Cells were incubated for 48 h with increasing concentrations of the Ni compounds or vehicle (12 concentrations, 0–1 mM).…”

Section: Methodsmentioning

confidence: 99%

“…The measurement of β-catenin was determined using a commercially available kit for measuring human β-catenin in cell lysates (MyBioSource, Inc. #MBS266009; San Diego, CA, USA) and used as it has described in our previously published data based on the manufacturer’s protocol [ 60 ]. β-catenin was quantified by measuring the absorbance at 450 nm and extrapolating to the standard curve.…”

Section: Methodsmentioning

confidence: 99%

“…Exposure was initiated by the addition of 50 μM NiCl 2 , Ni-acetate or vehicle for 48 h in a 37 °C/5% CO 2 incubator. After exposure, caspase 3/7 activity was determined as it has described previously [ 60 ]. Emitted fluorescence was measured using a Bio-Tek ® plate reader and Gen5 software at 485 ex /530 em .…”

Section: Methodsmentioning

confidence: 99%

“…RNU6-snRNA was used as reference RNA to normalise miR expression levels, forward, 5′-GCTTCGGCAGCACATATACTAAAAT-3′ and reverse 5′-CGCTTCACGAATTTGCGTGTCAT-3. The conditions for thermocycling were as described previously [ 60 ]. The miR-155, miR-126, and miR-221 expression levels were normalised to RNU6 using the 2^ ΔΔCT method [ 61 ].…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies have shown that environmental toxins, such as Cd, can promote their toxicity through miRs [ 12 , 18 , 60 ]. Toxic metals such as Ni have not been studied as extensively as Cd, and, therefore, only a small number of miRs associated with Ni exposure has been characterized.…”

Section: Introductionmentioning

confidence: 99%

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Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs

Mortoglou

Manić

Djordjevic

et al. 2022

Toxics

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nickel’s Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs

Mortoglou

Manić

Djordjevic

et al. 2022

Toxics

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Trace elements in pancreatic cancer

Yanjun,

Jing,

Yifei

et al. 2024

Cancer Medicine

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BackgroundPancreatic cancer (PCA) is an extremely aggressive malignant cancer with an increasing incidence and a low five‐year survival rate. The main reason for this high mortality is that most patients are diagnosed with PCA at an advanced stage, missing early treatment options and opportunities. As important nutrients of the human body, trace elements play an important role in maintaining normal physiological functions. Moreover, trace elements are closely related to many diseases, including PCA.ReviewThis review systematically summarizes the latest research progress on selenium, copper, arsenic, and manganese in PCA, elucidates their application in PCA, and provides a new reference for the prevention, diagnosis and treatment of PCA.ConclusionTrace elements such as selenium, copper, arsenic and manganese are playing an important role in the risk, pathogenesis, diagnosis and treatment of PCA. Meanwhile, they have a certain inhibitory effect on PCA, the mechanism mainly includes: promoting ferroptosis, inducing apoptosis, inhibiting metastasis, and inhibiting excessive proliferation.

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