scholarly journals Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 Genes Enhance Gastric Cancer Development in the Presence of Helicobacter Pylori

Author(s):  
Ufuk Demirci ◽  
Seda Orenay-Boyacioglu ◽  
Elmas Kasap ◽  
Emre Gerceker ◽  
Fahri Bilgic ◽  
...  

Abstract Introduction: Intestinal metaplasia (IM), and Helicobacter pylori (HP) infection can be shown as risk factors in the development of gastric cancer (GC). WNT signaling pathway plays a critical role in carcinogenesis. However, the literature studies are limited on the significance of this pathway for the transition from IM to GC.Methods: We aimed to investigate the importance of the genes of WNT signaling pathways diagnostic and prognostic markers in the presence and absence of HP in conversion from IM to GC. 104 patients, (GC group n=35, IM group n=45, control group n=25) were included in this case-control study. Expression of genes in WNT signalling were searched in study groups with qRT-PCR array and qRT-PCR method. Data were analysed using PCR array data analysis software.Results: Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in the GC and IM groups compared to the control group (p <0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was observed in patients with metastatic GC compared to patients with GC without metastasis (p <0.05). It was found that the RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes were statistically significantly over-expressed in diffuse GC patients compared to non-diffuse GC patients (p <0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in HP positive IM patients compared to HP negative IM patients (p <0.05).Conclusion: Overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes in IM may suggest that these genes are important markers in the development of IM and inflammation with HP. In addition, these genes are linked to tumor burden in the GC group. Consequently, we can conclude that these genes are poor prognosis biomarkers for GC and have the potential to be used as markers for future treatment monitoring.

2018 ◽  
Vol 1 (3) ◽  
pp. 17-35 ◽  
Author(s):  
Shahid Hussain Soomro ◽  
Jifu Jie ◽  
Hui Fu

Oligodendrocytes are specialized glial cell in central nervous system (CNS) responsible for the formation of myelin sheath around the axon. Oligodendrocyte proliferation and differentiation is regulated by Wnt signaling pathway, at various stages. However, different study groups have described controversial conclusions about the effect of Wnt on oligodendrocytes precursor cells (OPCs) development. Initially it has been proposed that Wnt pathway negatively regulates the OPCs proliferation and differentiation but recently some studies have described that Wnt promotes the differentiation of OPCs. After carefully reviewing the literature, we believe that Wnt play multiple roles in OPCs differentiation and its function is time (stage) and dose sensitive. Low to moderate activation of Wnt promotes OPC development, while too much or too low is inhibitory. Current evidences also suggested that in early developmental stages, Wnt inhibits the OPCs formation from neural progenitors and differentiation into immature oligodendrocytes. But in late stages Wnt plays promoting role in differentiation and maturation of oligodendrocytes. This review summarized the updated information regarding the critical role of Wnt signaling cascade in proliferation and differentiation of OPCs.


2020 ◽  
Author(s):  
Maryam Kianmehr ◽  
Ahmad Hormati ◽  
Mohsen Zargar ◽  
Roohollah Fateh ◽  
Razieh Nazari

Abstract Background: Some disease-specific Helicobacter pylori virulence genes can be used for predicting the outcome of diseases. Thus, the current study aimed to explore the frequency of the vacA, cagA, sabA, dupA, babA, oipA, and iceA1 genes in H. pylori isolates, and to determine whether any association exists between the expression of these genes and gastric cancer (GC).Methods: H. pylori isolates were collected from individuals with digestive diseases. The cagA, vacA, dupA, sabA, babA, oipA, and iceA1 genes were determined by PCR. The qRT-PCR was used for expression analysis of the tested genes. Results: The presence of the cagA, vacA, dupA, sabA, babA, oipA and iceA1 genes in H. pylori isolates were 41.3%, 95.5%, 31.0%, 93.1%, 55.1%, 82.7%, and 62.0%, respectively. The cagA, dupA, and babA expression in the GC patients was statistically higher than that of the control group (P <0.05). Conclusions: Our results indicated a high diversity and frequency of H. pylori virulence genes among individuals with gastric diseases in the Iranian population. The cagA, dupA, and babA expression were significantly higher in the GC patients, thus, it may suggest that screening of these genes may help identify peoples at higher risk for GC.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Principia Scavo ◽  
Antonio Cigliano ◽  
Nicoletta Depalo ◽  
Elisabetta Fanizza ◽  
Maria Grazia Bianco ◽  
...  

Extracellular vesicles (EVs) are involved in intercellular communication during the carcinogenesis. Our attention has been focused on small EVs (sEVs) protein content in colorectal and gastric cancer (CRC and GC). Frizzled (FZD) proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in the carcinogenesis of CRC and GC. Here, the expression of a specific FZD protein, namely, FZD-10, was investigated in the sEVs extracted from plasma of patients affected by CRC and GC as involved in canonical and noncanonical Wnt signaling in cancer stem cells with a subsequent modification of cellular heterogeneity, omics reprogramming, and tumor plasticity. The expression of FZD-10 protein in the sEVs extracted from plasma of patients affected by CRC and GC and sEVs from plasma of healthy subjects was evaluated against the level of protein Hsp70, established as EVs specific markers along with CD63 and ALIX proteins. The FZD-10 extract from sEVs isolated from plasma of the controls and the CRC or GC subjects indicated that its expression in oncological patients was higher than in the control group, while, at the end of the treatment, it reached values comparable with the average level of controls. Furthermore, the level of FZD-10 in the whole plasma was found comparable with its level in the sEVs extract. The level of FZD-10 in the sEVs represents a potential reliable biomarker with a valuable prognostic function for the diagnosis of CRC and GC and for monitoring the treatment response.


2011 ◽  
pp. 81-87
Author(s):  
Thi Thu Huong Hoang ◽  
Minh Vuong Nguyen

Objectives: Studying on the variation in CA 72-4 levels of the gastric cancer’s patients before and after 10 days and 30 days surgery treatment. Materials and methods: The studying group included 42 gastric cancer’s patients who were examinated and treated in cancerology service of Hue University Hospital and gastroenterology service of Hue Central Hospital. The control group included 30 healthy normal examinated at Hue University Hospital. The study groups were clinical, endoscopic anatopathologic examination diagnosed with gastric cancer and quantitative levels of CA 72-4 in three times points: before surgerying, after surgerying 10 days and 30 days postoperatively. Rerults: The concentration of CA 72-4 in gastric cancer’s patients was 10.06 ± 16.49 U/ml. Clearly higher than the control group 1.2 ± 0.4 U/ml(p <0.01). The rate increased levels of CA 72-4 in gastric cancer’s patients before surgerying was 27.5% and the control group was 0%. After 10 days of surgery, CA 72-4 level was 5.56 ± 8.55 U/ml; 82.5% of patients have reduced levels of CA 72-4 and 17.5% no changes; there are 0% increased cases. After 30 days of surgery, CA 72-4 level was 3.79 ± 6,52 U/ml. CA 72-4 level 10 days after surgering have decreased significantly compared to before surgery (p < 0.05) and 30 days after surgery have decreased significantly compared to after 10 days (p < 0.05). 30 days postoperatively, 90% patients had reduced levels of CA 72-4, 10% no changes, no patient had increased levels of CA 72-4 and no patient be relapsed after 30 days of treatment. Conclusions: CA 72-4 concentrations before surgerying increased 27.5%, after surgery 10 days and 30 days reduced step by step, no case have increased CA 72-4 levels, no case relapsed after 30 days.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 522
Author(s):  
Dehua Liu ◽  
Chenyu Sun ◽  
Nahyun Kim ◽  
Chandur Bhan ◽  
John Pocholo Whitaker Tuason ◽  
...  

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P &lt; 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.


Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2833-2842 ◽  
Author(s):  
Claire M. Edwards ◽  
James R. Edwards ◽  
Seint T. Lwin ◽  
Javier Esparza ◽  
Babatunde O. Oyajobi ◽  
...  

There is increasing evidence to suggest that the Wnt signaling pathway plays a critical role in the pathogenesis of myeloma bone disease. In the present study, we determined whether increasing Wnt signaling within the bone marrow microenvironment in myeloma counteracts development of osteolytic bone disease. C57BL/KaLwRij mice were inoculated intravenously with murine 5TGM1 myeloma cells, resulting in tumor growth in bone and development of myeloma bone disease. Lithium chloride (LiCl) treatment activated Wnt signaling in osteoblasts, inhibited myeloma bone disease, and decreased tumor burden in bone, but increased tumor growth when 5TGM1 cells were inoculated subcutaneously. Abrogation of β-catenin activity and disruption of Wnt signaling in 5TGM1 cells by stable overexpression of a dominant-negative TCF4 prevented the LiCl-induced increase in subcutaneous growth but had no effect on LiCl-induced reduction in tumor burden within bone or on osteolysis in myeloma-bearing mice. Together, these data highlight the importance of the local microenvironment in the effect of Wnt signaling on the development of myeloma bone disease and demonstrate that, despite a direct effect to increase tumor growth at extraosseous sites, increasing Wnt signaling in the bone marrow microenvironment can prevent the development of myeloma bone disease and inhibit myeloma growth within bone in vivo.


2020 ◽  
Author(s):  
Luqi xue ◽  
E Yang ◽  
Jinhai Gou ◽  
Dan Nie ◽  
Tao Yi ◽  
...  

Abstract Background The pathogenesis and clinical behaviors between solitary uterine leiomyoma (SUL) and multiple uterine leiomyomas (MUL) vary, which lead to the difference in management for childbearing-aged patients. Herein, we aim to find the potential miRNAs involved in the development of SUL and MUL. Results The top 5 differentially expressed miRNAs, Wnt signalling pathway and its two central molecules APC and CTNNB1 were screened out according to microarray analysis and bioinformatics. MiR-142-3p was selected for further exploration. In validation of qRT-PCR, MiR-142-3p was significantly upregulated in SUL, while downregulated in MUL, CTNNB1 and sequencing target AXIN-2 were expressed at higher level in MUL than SUL. Overexpression of MiR-142-3p resulted in lower transcription level of CTNNB1 and AXIN-2, and lower cell proliferation level. Conclusions MiR-142-3p may be involved in the development of SUL and MUL by interacting with CTNNB1 and AXIN-2 through Wnt signaling pathway. MiR-142-3p could serve as a potential biomarker for individualized treatment between SUL and MUL in the future.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Chen ◽  
Lu Xu ◽  
Zhi-li Shan ◽  
Shu Chen ◽  
Hao Hu

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hua Zhang ◽  
Haitao Huang ◽  
Xiaomei Xu ◽  
Haiying Wang ◽  
Jianxiang Wang ◽  
...  

Abstract Background Gastric cancer (GC) is one common cancer which occurs in the stomach leading to high mortality around the world. Long non-coding RNAs (lncRNAs) were found overexpressed or silenced in the occurrence and progression of multiple cancers including GC. Method The gene expression level in GC tissues and cells were analyzed by RT-qPCR. CCK-8, colony formation, flow cytometry and transwell assays were performed for the function analysis of HLA complex group 11 (HCG11). The mechanism study for HCG11 was conducted using RIP, RNA pull down and luciferase reporter assays. Results HCG11 was discovered highly expressed in GC tissues and cells. Depletion experiments were used to evaluate HCG11 silence on cell proliferation, migration and apoptosis. Moreover, Wnt signaling pathway was found as a tumor promoter in GC. RIP assay, RNA pull down assay and luciferase reporter assay were performed to illustrate the relationship of HCG11, miR-1276 and CTNNB1. Rescue assays revealed that HCG11/miR-1276/CTNNB1 axis regulated the incidence and development of GC. Tumor formation in mice proved that HCG11 was negatively correlated with miR-1276 and had positively correlation with CTNNB1. Conclusion Overall, HCG11 accelerated proliferation and migration in GC through miR-1276/CTNNB1 and Wnt signaling pathway, revealing that HCG11 could be a brand new target for GC.


Sign in / Sign up

Export Citation Format

Share Document