scholarly journals Variances in the expression profile of histaminergic system in the endometroid endometrial cancer

2021 ◽  
Author(s):  
Robert Nowakowski ◽  
Beniamin Grabarek ◽  
Magdalena Gradzik ◽  
Paweł Ordon ◽  
Hanna Zientek ◽  
...  
Author(s):  
Robert Nowakowski ◽  
Beniamin Grabarek ◽  
Anna Burnat-Olech ◽  
Dariusz Boroń ◽  
Monika Paul-Samojedny

Background: This study aimed to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment. Methods: Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours compared to the untreated cells (control). The molecular analysis included extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay. Results: Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFβ1, SMAD3, FOXO8, whereas in EC-1A, they were mRNA TGFβ1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFβ1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment. Conclusion: Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFβ1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes.


2020 ◽  
Author(s):  
Beniamin Grabarek ◽  
Magdalena Mistarz ◽  
Mateusz Maziarz ◽  
Michał Szurgot ◽  
Weronika Wieczorek

Author(s):  
Nikola Zmarzły ◽  
Ewelina Hermyt ◽  
Celina Kruszniewska-Rajs ◽  
Joanna Gola ◽  
Andrzej Witek ◽  
...  

Background: Epithelial-mesenchymal transition (EMT) is a molecular reprogramming that leads to an increased ability to migrate, which can promote invasion and metastasis. EMT can be initiated in response to the activity of signaling pathways such as Wnt as well as miRNAs. Methods: The study material consisted of 50 endometrial samples: 40 with diagnosed endometrial cancer and 10 without neoplastic changes. Expression profile of EMT-related genes was assessed with microarrays and validated by RT-qPCR. MicroRNA expression profiling was performed using microarrays. It was also determined which miRNAs may participate in the expression regulation of EMT-related genes. Results: CDH1 overexpression was observed in all three endometrial cancer grades using both mRNA microarrays and RTqPCR. Microarray experiment showed a decrease in CDH2 level regardless of the endometrial cancer grade, however it was only partially validated with RT-qPCR. Low levels of WNT2, WNT4, WNT5A have also been observed. Decreased expression of WNT2 and WNT5A may be caused by miR-331-3p and miR-200b-5p, respectively. Conclusions: The Wnt signaling is disrupted in endometrial cancer, which may be due to miR-331-3p and miR-200b-5p activity. In addition, a change in WNT5A level in endometrial cancer compared to control may indicate that it acts as a suppressor gene and that its low expression is associated with tumor progression.


2019 ◽  
Vol 20 (23) ◽  
pp. 6011
Author(s):  
Ewelina Hermyt ◽  
Nikola Zmarzły ◽  
Beniamin Grabarek ◽  
Celina Kruszniewska-Rajs ◽  
Joanna Gola ◽  
...  

Endometrial cancer develops as a result of abnormal cell growth associated with uncontrolled cell proliferation, excessive activation of signaling pathways and miRNA activity. The aim of this study was to determine the expression profile of genes associated with cell proliferation and to assess which miRNAs can participate in the regulation of their expression. The study enrolled 40 patients with endometrial cancer and 10 patients without neoplastic changes. The expression profile of genes associated with cell proliferation and the expression profile of miRNAs were assessed using microarrays. RT-qPCR was performed to validate mRNA microarray results. The mirTAR tool was used to identify miRNAs that regulate the activity of genes associated with cell proliferation. Decreased expression of IGF1 and MYLK, as well as SOD2 overexpression, were observed in endometrial cancer using both mRNA microarrays and RT-qPCR. Microarray analysis showed low levels of NES and PRKCA, but this was only partially validated using RT-qPCR. Reduced activity of MYLK may be caused by increased miR-200c, miR-155 and miR-200b expression. Cell proliferation is disturbed in endometrial cancer, which may be associated with an overexpression of miR-200a, miR-200c, and miR-155, making it a potential diagnostic marker.


2009 ◽  
Vol 7 (2) ◽  
pp. 454
Author(s):  
R.A. Tassi ◽  
E.R. Siegel ◽  
E. Bignotti ◽  
A. Ravaggi ◽  
P. Todeschini ◽  
...  

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Tiphaine de Foucher ◽  
Maria Sbeih ◽  
Jenifer Uzan ◽  
Sofiane Bendifallah ◽  
Marine Lefevre ◽  
...  

2021 ◽  
Vol 10 (13) ◽  
pp. 2787
Author(s):  
Dariusz Boroń ◽  
Robert Nowakowski ◽  
Beniamin Oskar Grabarek ◽  
Nikola Zmarzły ◽  
Marcin Opławski

The identification of novel molecular markers and the development of cancer treatment strategies are very important as cancer incidence is still very high. Obesity can contribute to cancer progression, including endometrial cancer. Adipocytes secrete leptin, which, when at a high level, is associated with an increased risk of cancer. The aim of this study was to determine the expression profile of leptin-related genes in the endometrial tissue samples and whole blood of patients. The study material included tissue samples and whole blood collected from 30 patients with endometrial cancer and 30 without cancer. Microarrays were used to assess the expression profile of leptin-related genes. Then, the expression of leptin (LEP), leptin receptor (LEPR), leptin receptor overlapping transcript (LEPROT), and leptin receptor overlapping transcript-like 1 (LEPROTL1) was determined by the Real-Time Quantitative Reverse Transcription Reaction (RT-qPCR). The serum leptin concentration was evaluated using Enzyme-linked immunosorbent assay (ELISA). Leptin and its receptors were overexpressed both at the mRNA and protein levels. Furthermore, there were strong positive correlations between leptin levels and patient Body Mass Index (BMI). Elevated levels of leptin and its receptors may potentially contribute to the progression of endometrial cancer. These observations may be useful in designing endometrial cancer treatment strategies.


2020 ◽  
Vol 21 (12) ◽  
pp. 1242-1248
Author(s):  
Robert Kiełabsiński ◽  
Przemysław Kieszkowski ◽  
Beniamin O. Grabarek ◽  
Dariusz Boroń

Background: A reduced concentration of adiponectin is considered as an independent factor of the risk of inducing endometrial cancer. Cisplatin is a drug used in the therapy of this type of neoplasm. However, knowledge of the effects of cisplatin on the adiponectin level is still limited. Objective: he purpose of this study was to assess the impact of cisplatin depending on the concentration and time of exposition of the cells to the drug on the adiponectin level in the endometrial cancer cell line. Methods: : Cells of endometrial cancer cell line Ishikawa were exposed for 12,24 and 48 hour periods to cisplatin with the following concentrations: 2.5μM, 5μM, 10μM. The changes in the expression profile of adiponectin were compared to the RtqPCR reaction and ELISA test. The STATISTICA 13.0 PL program was used for statistical analysis (p<0.05). Results: : In the culture without the drug, the concentration of adiponectin was statistically lower than in the cell culture incubated with the drug. Changes on the mRNA level seem to be more specific than on the protein level, although in both cases, the same trend in the expression changes was noted. Discussion: The longer the time of exposition of the cells to the drug, the expression of mRNA, and the adiponectin protein increased. Changes in the expression profile were characterized statistically (p<0.05). Conclusion: Cisplatin, in a noticeable way, changes the expression profile of adiponectin. Molecular analysis indicated that in the case of endometrial cancer therapy should be implemented with a concentration of no less than 5 μM.


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