scholarly journals Reverse Regulation Between sFRP 5 and Dkk 1 Gene in Early Stage Lung Adenocancer

2021 ◽  
Author(s):  
Arife Zeybek ◽  
Necdet Oz ◽  
Serdar Kalemci ◽  
Kursad Tosun ◽  
Tuba Gökdoğan Edgünlü ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tumor Tissue ◽  
Early Stage ◽  
Wnt Signaling Pathway ◽  
Normal Lung ◽  
Pcr Analysis ◽  
Related Protein ◽  
Expression Levels

Abstract Purpose: We aimed to examine the expression levels of the genes of APC (Adenomatous Polyposis Coli) 1, APC 2, Dkk (Dickkopf related protein) 1, Dkk -3, sFRP (Secreted frizzled-related protein) -2, sFRP-4, and sFRP-5 genes which play a role in the Wnt signaling pathway in lung adenocarcinoma and adjacent normal lung tissues, and to evaluate their relationship with clinical-pathological factors.Materials and methods: Between 2011 and 2018, the expression levels of the relevant genes in formalin-fixed paraffin-embedded tumor and adjacent intact lung tissue samples of 57 patients who were operated for lung adenocarcinoma were determined by Real-time PCR analysis. Results: The expression levels of the Dkk-1 gene in the tumor tissue, especially in stage I-II, were statistically significantly suppressed compared to normal tissue (p <0.025 ). Although Dkk-1 gene expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, the level of expression of the sFRP-5 gene was found to be statistically significantly higher (p<0.039). Conclusion: In our study, between the sFRP-5 and Dkk-1 genes, known as the extracellular antagonist of the Wnt signaling pathway was found the reverse regulation. sFRP-5 gene was found as having an oncogenic role in adenocarcinoma development. Reverse regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. For that reason, clinically, this relationship needs to research in a larger series of pure adenocarcinoma and normal human lung tissues, separated by its stage, for potential therapeutic target or prognostic its significance.

scholarly journals Analysis of microRNA expression in CD133 positive cancer stem‑like cells of human osteosarcoma cell line MG-63

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12115
Author(s):  
Xiong Shu ◽  
Weifeng Liu ◽  
Huiqi Liu ◽  
Hui Qi ◽  
Chengai Wu ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Pcr Analysis ◽  
Pathway Enrichment Analysis ◽  
Osteosarcoma Cell ◽  
Expression Levels

Osteosarcoma (OS) is a primary malignant tumor of bone occurring in young adults. OS stem cells (OSCs) play an important role in the occurrence, growth, metastasis, drug resistance and recurrence of OS. CD133 is an integral membrane glycoprotein, which has been identified as an OSC marker. However, the mechanisms of metastasis, chemoresistance, and progression in CD133(+) OSCs need to be further explored. In this study, we aim to explore differences in miRNA levels between CD133(+) and CD133(−) cells from the MG-63 cell line. We found 20 differentially expressed miRNAs (DEmiRNAs) (16 upregulated and 4 downregulated) in CD133(+) cells compared with CD133(−) cells. Hsa-miR-4485-3p, hsa-miR-4284 and hsa-miR-3656 were the top three upregulated DEmiRNAs, while hsa-miR-487b-3p, hsa-miR-493-5p and hsa-miR-431-5p were the top three downregulated DEmiRNAs. In addition, RT-PCR analysis confirmed that the expression levels of hsa-miR-4284, hsa-miR-4485-3p and hsa-miR-3656 were significantly increased, while the expression levels of hsa-miR-487b-3p, hsa-miR-493-5p, and hsa-miR-431-5p were significantly decreased in CD133(+) cells compared with CD133(−) cells. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that predicted or validated target genes for all 20 DEmiRNAs or the selected 6 DEmiRNAs participated in the “PI3K-Akt signaling pathway,” “Wnt signaling pathway,” “Rap1 signaling pathway,” “Cell cycle” and “MAPK signaling pathway”. Among the selected six DEmiRNAs, miR-4284 was especially interesting. MiR-4284 knockdown significantly reduced the sphere forming capacity of CD133(+) OS cells. The number of invasive CD133(+) OS cells was markedly decreased after miR-4284 knockdown. In addition, miR-4284 knockdown increased the p-β-catenin levels in CD133(+) OS cells. In conclusion, RNA-seq analysis revealed DEmiRNAs between CD133(+) and CD133(−) cells. MiRNAs might play significant roles in the function of OSCs and could serve as targets for OS treatment. MiR-4284 prompted the self-renewal and invasion of OSCs. The function of miR-4284 might be associated with the Wnt signaling pathway.

scholarly journals Secreted frizzled related protein 1 protects H9C2 cells from hypoxia/re-oxygenation injury by blocking the Wnt signaling pathway

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Jing Tao ◽  
Mayila Abudoukelimu ◽  
Yi-tong Ma ◽  
Yi-ning Yang ◽  
Xiao-mei Li ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
H9c2 Cells ◽  
Related Protein

Different Activation of WNT Signaling Pathway in B-Cell and T-Cell Acute Leukemias.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4317-4317
Author(s):  
Muge Sayitoglu ◽  
Ozden Hatirnaz ◽  
Yucel Erbilgin ◽  
Fatmahan Atalar ◽  
Ugur Ozbek
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Wnt Signaling ◽  
B Cell ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Wnt Signaling Pathway ◽  
Hematopoietic Cells ◽  
Expression Levels

Abstract WNT signaling pathway proteins function as hematopoietic growth factors and regulate proliferation in normal T-cell and B-cell development. Recent experimental evidence demonstrated that oncogenic transformation in leukemias of both lymphoid and myeloid lineages is dependent on WNT signaling. Not much is known about activation of WNT signaling pathway, its ligands and receptors in hematopoiesis and leukemia pathogenesis. To define its role in leukemia, we aimed to determine mRNA levels of the critical members of WNT pathway (WNT5A, WNT10B, FZ5, β catenin, APC, TCF-1 and LEF-1) by using quantitative real time PCR in acute lymphoblastic leukemia (ALL) patients (T-cell n=42, B-cell n=46 and pre B-cell n=30) and normal hematopoietic cells (bone marrow n=6, peripheral blood n=10, and CD19+ cells from peripheral blood). These genes expressed varying levels in B-cells, preB-cells and T-cells. In the B-cell leukemia patients, WNT5A was expressed notably (OR=58.05 CI 95% 1.63–1219.55, p&gt;0,001). WNT5A directs Ca++ dependent signaling by PKC and a G protein dependent manner which is an alternative pathway for beta-catenin mediated signaling. Also LEF-1 levels were higher in B-ALL patients and APC expression was down regulated when compared to normal tissue (OR=18.81 CI 95% 0.34–5703, p&gt;0.001 and OR=0.212 CI 95% 0.006–8.816, p=0.001, respectively). It is known that LEF-1 blocks APC mediated β catenin nuclear export and activates transcription of various transforming genes, including cyclin, D1, c-myc, MMP7, and LEF-1 itself. WNT5A or WNT10B proteins were not found to be up regulated in preB-ALL whereas APC and LEF-1 gene expressions were increased compared to normal hematopoietic cells (OR=32.97 CI 95% 0.27–1281, 38 p&gt;0.001 and OR=5.57 CI 95% 0.28–89.51, p=0.01, respectively). We found increased TCF-1 expression (7.4 fold) without any β catenin accumulation in T-ALL patients. It is known that TCF-1 in absence of β catenin functions as a tumor suppressor gene. WNT5A, APC and LEF-1 gene expression levels were also different between T-cell, B-cell and preB cell ALL cases. WNT5A expression had the highest levels in B-ALL compared to T-ALL cases, whereas the highest APC expression levels were observed in preB and T-ALL patients. Also LEF-1 expression levels were significantly different between preB and T-cell ALL patients. Taken together these results indicate that WNT signaling genes have abnormal expression and are active in acute lymphoblastic leukemia. This data suggests different WNT activation mechanisms exist in the leukemic transformation in different hematopoietic cells.

Combination of Salinomycin and AZD3463 Reveals Synergistic Effect on Reducing the Viability of T98G Glioblastoma Cells

2020 ◽  
Vol 20 (18) ◽  
pp. 2267-2273 ◽  
Author(s):  
Aycan Asik ◽  
Neslihan P.O. Ay ◽  
Bakiye G. Bagca ◽  
Hasan O. Caglar ◽  
Cumhur Gunduz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Synergistic Effect ◽  
Wnt Signaling ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Combination Treatment ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Expression Levels ◽  
Induced Apoptosis

Background: Salinomycin, an ionophore antibiotic, is known to be an effective agent in reducing the viability of Glioblastoma (GBM) cells. The combination of salinomycin with other chemotherapeutic drugs would help to overcome the drug resistance of GBM cells. Objective: This study aims to test the combinatorial effect of salinomycin and AZD3463 in T98G GBM cells. Methods: The cytotoxic effects of drugs on T98G GBM cells were determined by using WST-8 assay. Flow cytometry was used to identify apoptosis and cell cycle profiles after treatments. Real-time PCR was used to portray mRNA expression profiles of genes in the Wnt-signaling pathway after treatments. Results: IC50 concentrations of AZD3463 and salinomycin were 529nM and 7.3μM for 48h, respectively. The combination concentrations of AZD3463 and salinomycin were 3.3μM and 333nM, respectively. The combination treatment showed a synergistic effect on reducing the viability of GBM cells. AZD3463, salinomycin, and their combination induced apoptosis in 1.2, 1.4, and 3.2 folds, respectively. AZD3463 and the combination treatment induced the cell cycle arrest at the G1 phase. Salinomycin and AZD3463 treatments, either alone or in combination, resulted in the downregulation or upregulation of mRNA expression levels of genes in the Wntsignaling pathway. Conclusion: Salinomycin, AZD3463, and their combination may inhibit proliferation and induce apoptosis in GBM cells due to a decrease in expression levels of genes acting in both the canonical and non-canonical Wnt signaling pathways. The Wnt signaling pathway may be involved in salinomycin-AZD3463 drug interaction.

scholarly journals Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer

2018 ◽  
Author(s):  
Lijing Zhang ◽  
Xiaobo Sun ◽  
Jianyong Si ◽  
Guangzhi Li ◽  
Li Cao
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Gastric Epithelium ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Ferula Sinkiangensis ◽  
Gsk 3Β

AbstractThe traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. Thein vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.

scholarly journals Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nan Gao ◽  
Baoguo Ye
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Biological Function ◽  
Wnt Signaling Pathway ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Lung adenocarcinoma (LUAD), a widespread histopathological subtype of lung cancer, is deemed as a malignant tumor with a peak risk of mortality. Emerged as RNA with a loop structure that depleted protein coding ability, circular RNA (circRNA) has been identified as a regulator in cancer progression. Circ-SOX4, identified as a novel circRNA, has not been studied in any cancer yet. Thus, the regulatory function that circ-SOX4 exerts on LUAD development remains obscure. Aim of the study This study aimed to investigate the biological function and molecular mechanism of circ-SOX4 in LUAD. Methods The expression of circ-SOX4 was detected by qRT-PCR. CCK-8, colony formation, transwell and wound healing assays were performed to explore the biological function of circ-SOX4 in LUAD. The interaction between miR-1270 and circ-SOX41 (or PLAGL2) was confirmed by RNA pull down, luciferase reporter and RIP assays. Results Circ-SOX4 was found to be obviously upregulated in LUAD tissues and cells, and knockdown of it inhibited cell proliferation, invasion and migration in LUAD. Furthermore, silenced circ-SOX4 also inhibited LUAD tumor growth. Molecular mechanism assays revealed that circ-SOX4 interacted with miR-1270 in LUAD. Besides, PLAGL2 was confirmed as a downstream gene of miR-1270. Rescue assays validated that miR-1270 suppression or PLAGL2 overexpression countervailed circ-SOX4 depletion-mediated inhibition on cell proliferation, invasion and migration in LUAD. Additionally, it was discovered that circ-SOX4/miR-1270/PLAGL2 axis activated WNT signaling pathway in LUAD. Conclusions Circ-SOX4 boosted the development of LUAD and activate WNT signaling pathway through sponging miR-1270 and modulating PLAGL2, which provided a valuable theoretical basis for exploring underlying therapeutic target in LUAD.

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