Abstract
Background
Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification.
Methods and results
The top 10 OS hub genes—CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A—were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis.
Conclusions
TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway.
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Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.
Code Availability
Not applicable.
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Funding was provided by the Science and Technology Bureau of Lanzhou (Grant No. 2018-3-79).
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Y-DC, C-XY and Z-HY conceived and designed the idea to this paper; L-MQ, G-XD, G-TW, ZK, Z-XB, Z-RH and H-YC participated in its design and coordination and supervised the study. Y-DC, Y-DQ and Y-XL analyzed the data and revised the final paper. All authors read and approved the final version of the manuscript. Y-DC was the first author of this article, Y-DC and C-XY contributed equally to this work.
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Our study was approved by the ethics committee of the Second Hospital of Lanzhou University (Project Number: 2021 A-407).
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Yu, DC., Chen, XY., Zhou, HY. et al. TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells. Mol Biol Rep 49, 3055–3064 (2022). https://doi.org/10.1007/s11033-022-07133-6
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DOI: https://doi.org/10.1007/s11033-022-07133-6