INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation
Abstract Background Osteosarcoma (OS) is a refractory malignancy. This study aimed to explore the roles and mechanisms of Inhibin subunit beta A (INHBA) in OS. Methods INHBA expression levels in OS tissues and cells were assessed using RT-qPCR and western blotting. The impact of INHBA silencing on O...
| Główni autorzy: | , , , , , |
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| Format: | Artykuł |
| Język: | English |
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BMC
2023-11-01
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| Seria: | Journal of Orthopaedic Surgery and Research |
| Hasła przedmiotowe: | |
| Dostęp online: | https://doi.org/10.1186/s13018-023-04330-2 |
| _version_ | 1827764323650371584 |
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| author | Hongyu Zhang Yuemei Huang Qiuting Wen Yan Li Lin Guo Na Ge |
| author_facet | Hongyu Zhang Yuemei Huang Qiuting Wen Yan Li Lin Guo Na Ge |
| author_sort | Hongyu Zhang |
| collection | DOAJ |
| description | Abstract Background Osteosarcoma (OS) is a refractory malignancy. This study aimed to explore the roles and mechanisms of Inhibin subunit beta A (INHBA) in OS. Methods INHBA expression levels in OS tissues and cells were assessed using RT-qPCR and western blotting. The impact of INHBA silencing on OS development was then explored by transfecting the OS cell lines U2OS and MG63 with INHBA-small interfering RNA (siRNA). The influence of INHBA silencing on U2OS and MG63 cell proliferation, migration, and invasion was examined using MTT and Transwell assays. Epithelial–mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) were analyzed by RT-qPCR. The expression of genes involved in cell proliferation, migration, invasion, and the TGF-β signaling pathway was evaluated by western blotting and RT-qPCR. Results INHBA levels were elevated in the OS tissues and cells. Furthermore, the transforming growth factor-β (TGF-β) signaling pathway of OS cells was suppressed in response to INHBA-siRNA, whereas proliferation, migration, and invasion of OS cells were inhibited. Besides, INHBA-siRNA significantly inhibited OS cell EMT, evidenced by enhanced E-cadherin mRNA expression and reduced N-cadherin mRNA expression. Further mechanistic studies revealed that the TGF-β1 agonist SRI-011381 hydrochloride increased OS cell proliferation, migration, and invasion after INHBA downregulation. Conclusion We found that INHBA silencing could play a vital role in OS via TGF-β1-regulated proliferation, migration, and invasion. |
| first_indexed | 2024-03-11T11:02:45Z |
| format | Article |
| id | doaj.art-e60280a774e343e89a754a1d75cedfd4 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-11T11:02:45Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-e60280a774e343e89a754a1d75cedfd42023-11-12T12:24:37ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-11-0118111310.1186/s13018-023-04330-2INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activationHongyu Zhang0Yuemei Huang1Qiuting Wen2Yan Li3Lin Guo4Na Ge5Second Department of Orthopaedics, The Third Affiliated Hospital of Qiqihar Medial UniversityWuzhou Red Cross HospitalDepartment of Clinical Pathology, College of Qiqihar Medical UniversityThe First Hospital of QiqiharSecond Department of Orthopaedics, The Third Affiliated Hospital of Qiqihar Medial UniversityDepartment of Radiology, The Third Affiliated Hospital of Qiqihar Medial UniversityAbstract Background Osteosarcoma (OS) is a refractory malignancy. This study aimed to explore the roles and mechanisms of Inhibin subunit beta A (INHBA) in OS. Methods INHBA expression levels in OS tissues and cells were assessed using RT-qPCR and western blotting. The impact of INHBA silencing on OS development was then explored by transfecting the OS cell lines U2OS and MG63 with INHBA-small interfering RNA (siRNA). The influence of INHBA silencing on U2OS and MG63 cell proliferation, migration, and invasion was examined using MTT and Transwell assays. Epithelial–mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) were analyzed by RT-qPCR. The expression of genes involved in cell proliferation, migration, invasion, and the TGF-β signaling pathway was evaluated by western blotting and RT-qPCR. Results INHBA levels were elevated in the OS tissues and cells. Furthermore, the transforming growth factor-β (TGF-β) signaling pathway of OS cells was suppressed in response to INHBA-siRNA, whereas proliferation, migration, and invasion of OS cells were inhibited. Besides, INHBA-siRNA significantly inhibited OS cell EMT, evidenced by enhanced E-cadherin mRNA expression and reduced N-cadherin mRNA expression. Further mechanistic studies revealed that the TGF-β1 agonist SRI-011381 hydrochloride increased OS cell proliferation, migration, and invasion after INHBA downregulation. Conclusion We found that INHBA silencing could play a vital role in OS via TGF-β1-regulated proliferation, migration, and invasion.https://doi.org/10.1186/s13018-023-04330-2INHBAOsteosarcomaCell proliferation, migration, and invasionTGF-β signaling pathway |
| spellingShingle | Hongyu Zhang Yuemei Huang Qiuting Wen Yan Li Lin Guo Na Ge INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation Journal of Orthopaedic Surgery and Research INHBA Osteosarcoma Cell proliferation, migration, and invasion TGF-β signaling pathway |
| title | INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation |
| title_full | INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation |
| title_fullStr | INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation |
| title_full_unstemmed | INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation |
| title_short | INHBA gene silencing inhibits proliferation, migration, and invasion of osteosarcoma cells by repressing TGF-β signaling pathway activation |
| title_sort | inhba gene silencing inhibits proliferation migration and invasion of osteosarcoma cells by repressing tgf β signaling pathway activation |
| topic | INHBA Osteosarcoma Cell proliferation, migration, and invasion TGF-β signaling pathway |
| url | https://doi.org/10.1186/s13018-023-04330-2 |
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