Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA
Abstract Background The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC. Methods FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blottin...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-10-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-03100-0 |
| _version_ | 1819008984659525632 |
|---|---|
| author | Rulan Ma Kun Zhu Dawei Yuan Meijun Gong Yijun Li Kang Li Lei Meng |
| author_facet | Rulan Ma Kun Zhu Dawei Yuan Meijun Gong Yijun Li Kang Li Lei Meng |
| author_sort | Rulan Ma |
| collection | DOAJ |
| description | Abstract Background The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC. Methods FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43. Results FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells. Conclusion Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC. |
| first_indexed | 2024-12-21T00:49:09Z |
| format | Article |
| id | doaj.art-cb946d166ebe40409be3d0afd6576d6c |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T00:49:09Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-cb946d166ebe40409be3d0afd6576d6c2022-12-21T19:21:26ZengBMCJournal of Translational Medicine1479-58762021-10-0119111210.1186/s12967-021-03100-0Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNARulan Ma0Kun Zhu1Dawei Yuan2Meijun Gong3Yijun Li4Kang Li5Lei Meng6Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC. Methods FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43. Results FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells. Conclusion Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.https://doi.org/10.1186/s12967-021-03100-0Breast cancerFBXO43PCNALentivirusTumor growth |
| spellingShingle | Rulan Ma Kun Zhu Dawei Yuan Meijun Gong Yijun Li Kang Li Lei Meng Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA Journal of Translational Medicine Breast cancer FBXO43 PCNA Lentivirus Tumor growth |
| title | Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA |
| title_full | Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA |
| title_fullStr | Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA |
| title_full_unstemmed | Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA |
| title_short | Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA |
| title_sort | downregulation of the fbxo43 gene inhibits tumor growth in human breast cancer by limiting its interaction with pcna |
| topic | Breast cancer FBXO43 PCNA Lentivirus Tumor growth |
| url | https://doi.org/10.1186/s12967-021-03100-0 |
| work_keys_str_mv | AT rulanma downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna AT kunzhu downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna AT daweiyuan downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna AT meijungong downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna AT yijunli downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna AT kangli downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna AT leimeng downregulationofthefbxo43geneinhibitstumorgrowthinhumanbreastcancerbylimitingitsinteractionwithpcna |