NDLI: PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin

Content Provider	Springer Nature : BioMed Central
Author	Si, Zhenxing Shen, Zilong Luan, Feiyu Yan, Jinglong
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.
Related Links	https://josr-online.biomedcentral.com/counter/pdf/10.1186/s13018-023-03615-w.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13018-023-03615-w
Journal	Journal of Orthopaedic Surgery and Research
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2023-02-23
Access Restriction	Open
Subject Keyword	Orthopedics Surgical Orthopedics Osteosarcoma PINK1 FOXO3a Apoptosis Cisplatin
Content Type	Text
Resource Type	Article
Subject	Surgery Orthopedics and Sports Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3/2023

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