Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer
Bladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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Nature Research
2023
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| _version_ | 1825938327810867200 |
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| author | Ahmad, Umar Abdullah, Syahril De, Ming Chau Suet, Lin Chia Yusoff, Khatijah Soon, Choy Chan Teng, Aik Ong Razack, Azad Hassan Veerakumarasivam, Abhi |
| author_facet | Ahmad, Umar Abdullah, Syahril De, Ming Chau Suet, Lin Chia Yusoff, Khatijah Soon, Choy Chan Teng, Aik Ong Razack, Azad Hassan Veerakumarasivam, Abhi |
| author_sort | Ahmad, Umar |
| collection | UPM |
| description | Bladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular mechanism(s) associated with the development of NDV persistent infection in bladder cancer, we used mRNA expression profiles of persistently infected bladder cancer cells to construct PPI networks. Based on paths and modules in the PPI network, the bridges were found mainly in the upregulated mRNA-pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling and downregulated mRNA-pathways of antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades in persistent TCCSUPPi cells. In persistent EJ28Pi cells, connections were identified mainly through upregulated mRNA-pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle and the downregulated mRNA-pathways of Wnt signalling, HTLV-I infection and pathways in cancers. These connections were mainly dependent on RPL8-HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1—TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the networks that include RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction networks identified several putative drug targets that could be used to disrupt the linkages between the modules and prevent bladder cancer cells from acquiring NDV persistent infection. This novel PPI network analysis of differentially expressed mRNAs of NDV persistently infected bladder cancer cell lines provide an insight into the molecular mechanisms of NDV persistency of infection in bladder cancers and the future screening of drugs that can be used together with NDV to enhance its oncolytic efficacy. |
| first_indexed | 2024-09-25T03:36:18Z |
| format | Article |
| id | upm.eprints-100208 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-09-25T03:36:18Z |
| publishDate | 2023 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | upm.eprints-1002082024-07-10T07:01:31Z http://psasir.upm.edu.my/id/eprint/100208/ Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer Ahmad, Umar Abdullah, Syahril De, Ming Chau Suet, Lin Chia Yusoff, Khatijah Soon, Choy Chan Teng, Aik Ong Razack, Azad Hassan Veerakumarasivam, Abhi Bladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular mechanism(s) associated with the development of NDV persistent infection in bladder cancer, we used mRNA expression profiles of persistently infected bladder cancer cells to construct PPI networks. Based on paths and modules in the PPI network, the bridges were found mainly in the upregulated mRNA-pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling and downregulated mRNA-pathways of antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades in persistent TCCSUPPi cells. In persistent EJ28Pi cells, connections were identified mainly through upregulated mRNA-pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle and the downregulated mRNA-pathways of Wnt signalling, HTLV-I infection and pathways in cancers. These connections were mainly dependent on RPL8-HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1—TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the networks that include RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction networks identified several putative drug targets that could be used to disrupt the linkages between the modules and prevent bladder cancer cells from acquiring NDV persistent infection. This novel PPI network analysis of differentially expressed mRNAs of NDV persistently infected bladder cancer cell lines provide an insight into the molecular mechanisms of NDV persistency of infection in bladder cancers and the future screening of drugs that can be used together with NDV to enhance its oncolytic efficacy. Nature Research 2023-05-05 Article PeerReviewed Ahmad, Umar and Abdullah, Syahril and De, Ming Chau and Suet, Lin Chia and Yusoff, Khatijah and Soon, Choy Chan and Teng, Aik Ong and Razack, Azad Hassan and Veerakumarasivam, Abhi (2023) Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer. Scientific Reports, 13. art. no. 7323. pp. 1-12. ISSN 2045-2322 https://www.nature.com/articles/s41598-022-20521-z 10.1038/s41598-022-20521-z |
| spellingShingle | Ahmad, Umar Abdullah, Syahril De, Ming Chau Suet, Lin Chia Yusoff, Khatijah Soon, Choy Chan Teng, Aik Ong Razack, Azad Hassan Veerakumarasivam, Abhi Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer |
| title | Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer |
| title_full | Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer |
| title_fullStr | Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer |
| title_full_unstemmed | Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer |
| title_short | Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer |
| title_sort | analysis of ppi networks of transcriptomic expression identifies hub genes associated with newcastle disease virus persistent infection in bladder cancer |
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