Function and mechanism of GBP1 in the development and progression of cervical cancer
Abstract Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical can...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04837-6 |
| _version_ | 1797362950499991552 |
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| author | Senyu Wang Yajing Zhang Xiumin Ma Yangchun Feng |
| author_facet | Senyu Wang Yajing Zhang Xiumin Ma Yangchun Feng |
| author_sort | Senyu Wang |
| collection | DOAJ |
| description | Abstract Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer. |
| first_indexed | 2024-03-08T16:14:47Z |
| format | Article |
| id | doaj.art-df04e63190d64b65869a0774b09dd295 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-08T16:14:47Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-df04e63190d64b65869a0774b09dd2952024-01-07T12:42:08ZengBMCJournal of Translational Medicine1479-58762024-01-0122112510.1186/s12967-023-04837-6Function and mechanism of GBP1 in the development and progression of cervical cancerSenyu Wang0Yajing Zhang1Xiumin Ma2Yangchun Feng3Clinical Laboratory Center, Cancer Hospital Affiliated to Xinjiang Medical UniversityClinical Laboratory Center, Cancer Hospital Affiliated to Xinjiang Medical UniversityClinical Laboratory Center, Cancer Hospital Affiliated to Xinjiang Medical UniversityClinical Laboratory Center, Cancer Hospital Affiliated to Xinjiang Medical UniversityAbstract Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer.https://doi.org/10.1186/s12967-023-04837-6Guanylate binding protein 1 (GBP1)Tumor immunityCervical cancerAlternative splicing (AS)Cancer promotion |
| spellingShingle | Senyu Wang Yajing Zhang Xiumin Ma Yangchun Feng Function and mechanism of GBP1 in the development and progression of cervical cancer Journal of Translational Medicine Guanylate binding protein 1 (GBP1) Tumor immunity Cervical cancer Alternative splicing (AS) Cancer promotion |
| title | Function and mechanism of GBP1 in the development and progression of cervical cancer |
| title_full | Function and mechanism of GBP1 in the development and progression of cervical cancer |
| title_fullStr | Function and mechanism of GBP1 in the development and progression of cervical cancer |
| title_full_unstemmed | Function and mechanism of GBP1 in the development and progression of cervical cancer |
| title_short | Function and mechanism of GBP1 in the development and progression of cervical cancer |
| title_sort | function and mechanism of gbp1 in the development and progression of cervical cancer |
| topic | Guanylate binding protein 1 (GBP1) Tumor immunity Cervical cancer Alternative splicing (AS) Cancer promotion |
| url | https://doi.org/10.1186/s12967-023-04837-6 |
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