PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin
Abstract Background Osteosarcoma is a common primary bone malignancy prevalent among adolescents and young adults. PTEN-induced kinase 1 (PINK1) regulates Parkinson's disease, but its role in cancers is unknown. Objective This study was designed to analyze the mechanism by which PINK1 affects o...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-023-03615-w |
| _version_ | 1797864046216609792 |
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| author | Zhenxing Si Zilong Shen Feiyu Luan Jinglong Yan |
| author_facet | Zhenxing Si Zilong Shen Feiyu Luan Jinglong Yan |
| author_sort | Zhenxing Si |
| collection | DOAJ |
| description | Abstract Background Osteosarcoma is a common primary bone malignancy prevalent among adolescents and young adults. PTEN-induced kinase 1 (PINK1) regulates Parkinson's disease, but its role in cancers is unknown. Objective This study was designed to analyze the mechanism by which PINK1 affects osteosarcoma using bioinformatics and cell experiments. Materials and methods The gene expression profiles were downloaded from the TARGET database. Several online databases were used to analyze the expression and protein‒protein interaction networks. CCK-8 cell viability assays and cisplatin treatment were used to assess cell activity with or without cisplatin treatment. Acridine orange/ethidium bromide (AO/EB) fluorescence staining was used to calculate the percentage of apoptotic cells. Results Through bioinformatics analysis, we found that high expression of PINK1 was associated with poor prognosis in patients with osteosarcoma, and PINK1 inhibited apoptosis and promoted proliferation pathways. Next, we found that both PINK1 mRNA and protein levels were upregulated in osteosarcoma tissues. Additionally, we found that PTEN was reduced, while FOXO3a was markedly increased in osteosarcoma, suggesting that FOXO3a and not PTEN induced the overexpression of PINK1. CCK-8 and clonogenic assays showed that the knockdown of PINK1 decreased the growth of U2OS osteosarcoma cells. Ki67 immunofluorescence staining revealed that reduced cell proliferation in U2OS cells resulted in the depletion of PINK1. In addition, our AO/EB staining results indicated that the knockdown of PINK1 resulted in an increase in apoptotic cells and increased the levels of cleaved caspase-3. Furthermore, our experiments revealed that cisplatin promotes OS cell apoptosis by downregulating PINK1. Conclusion Collectively, our findings demonstrate that PINK1 is crucially involved in osteosarcoma and suggests that it can promote the apoptosis of OS cells as the downstream target gene of cisplatin. |
| first_indexed | 2024-04-09T22:46:20Z |
| format | Article |
| id | doaj.art-d661f482838b4007af5299090e71733f |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-09T22:46:20Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-d661f482838b4007af5299090e71733f2023-03-22T11:52:34ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-02-0118111110.1186/s13018-023-03615-wPINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatinZhenxing Si0Zilong Shen1Feiyu Luan2Jinglong Yan3Department of Emergency Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedic Department, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Emergency Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedic Department, The Second Affiliated Hospital of Harbin Medical UniversityAbstract Background Osteosarcoma is a common primary bone malignancy prevalent among adolescents and young adults. PTEN-induced kinase 1 (PINK1) regulates Parkinson's disease, but its role in cancers is unknown. Objective This study was designed to analyze the mechanism by which PINK1 affects osteosarcoma using bioinformatics and cell experiments. Materials and methods The gene expression profiles were downloaded from the TARGET database. Several online databases were used to analyze the expression and protein‒protein interaction networks. CCK-8 cell viability assays and cisplatin treatment were used to assess cell activity with or without cisplatin treatment. Acridine orange/ethidium bromide (AO/EB) fluorescence staining was used to calculate the percentage of apoptotic cells. Results Through bioinformatics analysis, we found that high expression of PINK1 was associated with poor prognosis in patients with osteosarcoma, and PINK1 inhibited apoptosis and promoted proliferation pathways. Next, we found that both PINK1 mRNA and protein levels were upregulated in osteosarcoma tissues. Additionally, we found that PTEN was reduced, while FOXO3a was markedly increased in osteosarcoma, suggesting that FOXO3a and not PTEN induced the overexpression of PINK1. CCK-8 and clonogenic assays showed that the knockdown of PINK1 decreased the growth of U2OS osteosarcoma cells. Ki67 immunofluorescence staining revealed that reduced cell proliferation in U2OS cells resulted in the depletion of PINK1. In addition, our AO/EB staining results indicated that the knockdown of PINK1 resulted in an increase in apoptotic cells and increased the levels of cleaved caspase-3. Furthermore, our experiments revealed that cisplatin promotes OS cell apoptosis by downregulating PINK1. Conclusion Collectively, our findings demonstrate that PINK1 is crucially involved in osteosarcoma and suggests that it can promote the apoptosis of OS cells as the downstream target gene of cisplatin.https://doi.org/10.1186/s13018-023-03615-wOsteosarcomaPINK1FOXO3aApoptosisCisplatin |
| spellingShingle | Zhenxing Si Zilong Shen Feiyu Luan Jinglong Yan PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin Journal of Orthopaedic Surgery and Research Osteosarcoma PINK1 FOXO3a Apoptosis Cisplatin |
| title | PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin |
| title_full | PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin |
| title_fullStr | PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin |
| title_full_unstemmed | PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin |
| title_short | PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin |
| title_sort | pink1 regulates apoptosis of osteosarcoma as the target gene of cisplatin |
| topic | Osteosarcoma PINK1 FOXO3a Apoptosis Cisplatin |
| url | https://doi.org/10.1186/s13018-023-03615-w |
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