The Evaluation of Gene Expression of GPR83, CA1, AWP1, and WTAP in AGS Cells Stimulated by the Helicobacter pylori cagC Gene

Journal of Cell and Molecular Research

مقاله 5، دوره 14، شماره 2 - شماره پیاپی 28، تیر 2023، صفحه 101-105   

نوع مقاله: Short Communication

شناسه دیجیتال (DOI): 10.22067/jcmr.2023.79168.1052

نویسندگان

Abbas Doosti^* ؛ Zahra Khoshfetrat

Department of Biology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

چکیده

              Gastric carcinoma (GC) is the third leading cause of malignancy-related deaths worldwide, and Helicobacter pylori is one of the identified causes of gastric cancer. The Cag pathogenicity island (cagA, cagC, virB2) is one of the major pathogens of H. pylori, which increased the risk of gastric cancer development. Some studies have shown that H. pylori significantly alters the expression of certain genes in gastric epithelial cells. This study aimed to investigate the expression of the GPR83, CA1, AWP1, and WTAP genes in AGS cells transfected with the recombinant pIRES2-EGFP-cagC vector. The pIRES2-EGFP-cagC and pIRES2-EGFP plasmids (as controls) were transfected into AGS cells by lipofectamine 2000 solution. Then, RNA extraction and cDNA synthesis were performed. The expression of GPR83, CA1, AWP1, and WTAP genes was evaluated using the real-time PCR method. Finally, the expression of each gene was evaluated using SPSS software and t-test independent statistical tests. Our findings indicated that the expression of the GPR83 gene in AGS cells treated with cagC statistically significantly increased compared to control cells (P=0.0327). On the contrary, the WTAP expression was significantly decreased (P=0.0132), whereas the AWP1 and CA1 mRNA expression levels were not statistically significant. This study shows that GPR83 and WTAP genes's expression in the host is significantly altered through cagC gene expression. Hence, it seems that the cagC gene's presence can explain some alterations in the expression of gastric epithelial cell genes and the cause of gastric cancer pathogenesis caused by H. pylori infection.

کلیدواژه‌ها

cagC gene؛ Gastric carcinoma؛ GPR83؛ Helicobacter pylori؛ WTAP

مراجع

Alfarouk K. O., Bashir A. H., Aljarbou A. N., Ramadan A. M., Muddathir A. K., AlHoufie S. T.,et al. (2019) The Possible Role of Helicobacter pylori in Gastric Cancer and Its Management. Frontiers in oncology 9:75.

Amieva M. and Peek Jr R. M. (2016) Pathobiology of Helicobacter pylori-Induced Gastric Cancer. Gastroenterology 150:64-78.

Assumpção P. P., Barra W. F., Ishak G., Coelho L. G. V., Coimbra F. J. F., Freitas H. C., et al. (2020) The diffuse-type gastric cancer epidemiology enigma. BMC gastroenterology 20:223.

Backert S. and Selbach M. (2008) Role of type IV secretion in Helicobacter pylori pathogenesis. Cellular microbiology 10:1573-1581.

Chang W.-L., Yeh Y.-C. and Sheu B.-S. (2018) The impacts of H. pylori virulence factors on the development of gastroduodenal diseases. Journal of biomedical science 25:68.

Churin Y., Al-Ghoul L., Kepp O., Meyer T. F., Birchmeier W. and Naumann M. (2003) Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. The Journal of cell biology 161:249-255.

Cover T. L., Lacy D. B. and Ohi M. D. (2020) The Helicobacter pylori Cag Type IV Secretion System. Trends in microbiology 28:682-695.

Craig L., Forest K. T. and Maier B. (2019) Type IV pili: dynamics, biophysics and functional consequences. Nature reviews. Microbiology 17:429-440.

De Witte C., Berlamont H. and Haesebrouck F. (2022) Helicobacter. Pathogenesis of Bacterial Infections in Animals:413-432.

Eusebi L. H., Telese A., Marasco G., Bazzoli F. and Zagari R. M. (2020) Gastric cancer prevention strategies: A global perspective. Journal of gastroenterology and hepatology 35:1495-1502.

Fan Y., Li X., Sun H., Gao Z., Zhu Z. and Yuan K. (2022) Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential. Biomolecules 12:1224.

Fischer W., Tegtmeyer N., Stingl K. and Backert S. (2020) Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function. Frontiers in microbiology 11:1592.

Guillemin K., Salama N. R., Tompkins L. S. and Falkow S. (2002) Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proceedings of the National Academy of Sciences of the United States of America 99:15136-15141.

Heidari F. and Doosti A. (2020) Evaluation of GPR83 Gene Expression in AGS Cells Transfected with Pflag-CMV-3-TagD Recombinant Vector. New Cellular and Molecular Biotechnology Journal 10:39-48.

Johnston F. M. and Beckman M. (2019) Updates on Management of Gastric Cancer. Current oncology reports 21:67.

Lim J. W., Kim H. and Kim K. H. (2003) Cell adhesion-related gene expression by Helicobacter pylori in gastric epithelial AGS cells. The international journal of biochemistry & cell biology 35:1284-1296.

Lin A. S., Dooyema S. D., Frick-Cheng A. E., Harvey M. L., Suarez G., Loh J. T., et al. (2020) Bacterial Energetic Requirements for Helicobacter pylori Cag Type IV Secretion System-Dependent Alterations in Gastric Epithelial Cells. Infection and immunity 88:e00790-00719.

Lueptow L. M., Devi L. A. and Fakira A. K. (2018) Targeting the Recently Deorphanized Receptor GPR83 for the Treatment of Immunological, Neuroendocrine and Neuropsychiatric Disorders. Progress in molecular biology and translational science 159:1-25.

Malfertheiner P., Megraud F., O'Morain C., Gisbert J., Kuipers E., Axon A., et al. (2017) Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 66:6-30.

Massarrat S. and Stolte M. (2014) Development of gastric cancer and its prevention. Archives of Iranian medicine 17:514-520.

Alfarouk K. O., Bashir A. H., Aljarbou A. N., Ramadan A. M., Muddathir A. K., AlHoufie S. T.,et al. (2019) The Possible Role of Helicobacter pylori in Gastric Cancer and Its Management. Frontiers in oncology 9:75.

Amieva M. and Peek Jr R. M. (2016) Pathobiology of Helicobacter pylori-Induced Gastric Cancer. Gastroenterology 150:64-78.

Assumpção P. P., Barra W. F., Ishak G., Coelho L. G. V., Coimbra F. J. F., Freitas H. C., et al. (2020) The diffuse-type gastric cancer epidemiology enigma. BMC gastroenterology 20:223.

Backert S. and Selbach M. (2008) Role of type IV secretion in Helicobacter pylori pathogenesis. Cellular microbiology 10:1573-1581.

Chang W.-L., Yeh Y.-C. and Sheu B.-S. (2018) The impacts of H. pylori virulence factors on the development of gastroduodenal diseases. Journal of biomedical science 25:68.

Churin Y., Al-Ghoul L., Kepp O., Meyer T. F., Birchmeier W. and Naumann M. (2003) Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. The Journal of cell biology 161:249-255.

Cover T. L., Lacy D. B. and Ohi M. D. (2020) The Helicobacter pylori Cag Type IV Secretion System. Trends in microbiology 28:682-695.

Craig L., Forest K. T. and Maier B. (2019) Type IV pili: dynamics, biophysics and functional consequences. Nature reviews. Microbiology 17:429-440.

De Witte C., Berlamont H. and Haesebrouck F. (2022) Helicobacter. Pathogenesis of Bacterial Infections in Animals:413-432.

Eusebi L. H., Telese A., Marasco G., Bazzoli F. and Zagari R. M. (2020) Gastric cancer prevention strategies: A global perspective. Journal of gastroenterology and hepatology 35:1495-1502.

Fan Y., Li X., Sun H., Gao Z., Zhu Z. and Yuan K. (2022) Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential. Biomolecules 12:1224.

Fischer W., Tegtmeyer N., Stingl K. and Backert S. (2020) Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function. Frontiers in microbiology 11:1592.

Guillemin K., Salama N. R., Tompkins L. S. and Falkow S. (2002) Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proceedings of the National Academy of Sciences of the United States of America 99:15136-15141.

Heidari F. and Doosti A. (2020) Evaluation of GPR83 Gene Expression in AGS Cells Transfected with Pflag-CMV-3-TagD Recombinant Vector. New Cellular and Molecular Biotechnology Journal 10:39-48.

Johnston F. M. and Beckman M. (2019) Updates on Management of Gastric Cancer. Current oncology reports 21:67.

Lim J. W., Kim H. and Kim K. H. (2003) Cell adhesion-related gene expression by Helicobacter pylori in gastric epithelial AGS cells. The international journal of biochemistry & cell biology 35:1284-1296.

Lin A. S., Dooyema S. D., Frick-Cheng A. E., Harvey M. L., Suarez G., Loh J. T., et al. (2020) Bacterial Energetic Requirements for Helicobacter pylori Cag Type IV Secretion System-Dependent Alterations in Gastric Epithelial Cells. Infection and immunity 88:e00790-00719.

Lueptow L. M., Devi L. A. and Fakira A. K. (2018) Targeting the Recently Deorphanized Receptor GPR83 for the Treatment of Immunological, Neuroendocrine and Neuropsychiatric Disorders. Progress in molecular biology and translational science 159:1-25.

Malfertheiner P., Megraud F., O'Morain C., Gisbert J., Kuipers E., Axon A., et al. (2017) Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 66:6-30.

Massarrat S. and Stolte M. (2014) Development of gastric cancer and its prevention. Archives of Iranian medicine 17:514-520.