Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer
Abstract Background Helicobacter pylori is a gastric pathogen that is responsible for causing chronic inflammation and increasing the risk of gastric cancer development. It is capable of persisting for decades in the harsh gastric environment because of the inability of the host to eradicate the inf...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6772 |
| _version_ | 1797371939661021184 |
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| author | Mahjerin Nasrin Reza Shahin Mahmud Nadim Ferdous Ishtiaque Ahammad Mohammad Uzzal Hossain Md. Al Amin A. K. M. Mohiuddin |
| author_facet | Mahjerin Nasrin Reza Shahin Mahmud Nadim Ferdous Ishtiaque Ahammad Mohammad Uzzal Hossain Md. Al Amin A. K. M. Mohiuddin |
| author_sort | Mahjerin Nasrin Reza |
| collection | DOAJ |
| description | Abstract Background Helicobacter pylori is a gastric pathogen that is responsible for causing chronic inflammation and increasing the risk of gastric cancer development. It is capable of persisting for decades in the harsh gastric environment because of the inability of the host to eradicate the infection. Several treatment strategies have been developed against this bacterium using different antibiotics. But the effectiveness of treating H. pylori has significantly decreased due to widespread antibiotic resistance, including an increased risk of gastric cancer. The small interfering RNAs (siRNA), which is capable of sequence‐specific gene‐silencing can be used as a new therapeutic approach for the treatment of a variety of such malignancies. In the current study, we rationally designed two siRNA molecules to silence the cytotoxin‐associated gene A (CagA) and vacuolating cytotoxin A (VacA) genes of H. pylori for their significant involvement in developing cancer. Methods We selected a common region of all the available transcripts from different countries of CagA and VacA to design the siRNA molecules. The final siRNA candidate was selected based on the results from machine learning algorithms, off‐target similarity, and various thermodynamic properties. Result Further, we utilized molecular docking and all atom molecular dynamics (MD) simulations to assess the binding interactions of the designed siRNAs with the major components of the RNA‐induced silencing complex (RISC) and results revealed the ability of the designed siRNAs to interact with the proteins of RISC complex in comparable to those of the experimentally reported siRNAs. Conclusion These designed siRNAs should effectively silence the CagA and VacA genes of H. pylori during siRNA mediated treatment in gastric cancer. |
| first_indexed | 2024-03-08T18:28:04Z |
| format | Article |
| id | doaj.art-c670455cee6d4007b7a03285db97f45d |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T18:28:04Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-c670455cee6d4007b7a03285db97f45d2023-12-30T08:53:26ZengWileyCancer Medicine2045-76342023-12-011224224072241910.1002/cam4.6772Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancerMahjerin Nasrin Reza0Shahin Mahmud1Nadim Ferdous2Ishtiaque Ahammad3Mohammad Uzzal Hossain4Md. Al Amin5A. K. M. Mohiuddin6Department of Biotechnology and Genetic Engineering, Life Science Faculty Mawlana Bhashani Science and Technology University Tangail BangladeshDepartment of Biotechnology and Genetic Engineering, Life Science Faculty Mawlana Bhashani Science and Technology University Tangail BangladeshDepartment of Biotechnology and Genetic Engineering, Life Science Faculty Mawlana Bhashani Science and Technology University Tangail BangladeshBioinformatics Division National Institute of Biotechnology Ashulia BangladeshBioinformatics Division National Institute of Biotechnology Ashulia BangladeshDepartment of Biotechnology and Genetic Engineering, Life Science Faculty Mawlana Bhashani Science and Technology University Tangail BangladeshDepartment of Biotechnology and Genetic Engineering, Life Science Faculty Mawlana Bhashani Science and Technology University Tangail BangladeshAbstract Background Helicobacter pylori is a gastric pathogen that is responsible for causing chronic inflammation and increasing the risk of gastric cancer development. It is capable of persisting for decades in the harsh gastric environment because of the inability of the host to eradicate the infection. Several treatment strategies have been developed against this bacterium using different antibiotics. But the effectiveness of treating H. pylori has significantly decreased due to widespread antibiotic resistance, including an increased risk of gastric cancer. The small interfering RNAs (siRNA), which is capable of sequence‐specific gene‐silencing can be used as a new therapeutic approach for the treatment of a variety of such malignancies. In the current study, we rationally designed two siRNA molecules to silence the cytotoxin‐associated gene A (CagA) and vacuolating cytotoxin A (VacA) genes of H. pylori for their significant involvement in developing cancer. Methods We selected a common region of all the available transcripts from different countries of CagA and VacA to design the siRNA molecules. The final siRNA candidate was selected based on the results from machine learning algorithms, off‐target similarity, and various thermodynamic properties. Result Further, we utilized molecular docking and all atom molecular dynamics (MD) simulations to assess the binding interactions of the designed siRNAs with the major components of the RNA‐induced silencing complex (RISC) and results revealed the ability of the designed siRNAs to interact with the proteins of RISC complex in comparable to those of the experimentally reported siRNAs. Conclusion These designed siRNAs should effectively silence the CagA and VacA genes of H. pylori during siRNA mediated treatment in gastric cancer.https://doi.org/10.1002/cam4.6772CagA and VacAgastric cancerHelicobacter pylorisiRNA |
| spellingShingle | Mahjerin Nasrin Reza Shahin Mahmud Nadim Ferdous Ishtiaque Ahammad Mohammad Uzzal Hossain Md. Al Amin A. K. M. Mohiuddin Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer Cancer Medicine CagA and VacA gastric cancer Helicobacter pylori siRNA |
| title | Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer |
| title_full | Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer |
| title_fullStr | Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer |
| title_full_unstemmed | Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer |
| title_short | Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer |
| title_sort | gene silencing of helicobacter pylori through newly designed sirna convenes the treatment of gastric cancer |
| topic | CagA and VacA gastric cancer Helicobacter pylori siRNA |
| url | https://doi.org/10.1002/cam4.6772 |
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