骨肉瘤是最常见的原发性恶性骨肿瘤，但其发病机制尚不清楚。据报道，泛素特异性加工肽酶 22 (USP22) 高度表达，并与肿瘤恶性程度和癌症预后相关。然而，USP22在骨肉瘤中的作用和机制尚不完全清楚。本研究旨在通过生物信息学分析结合实验验证来探讨USP22在骨肉瘤中的功能和潜在机制。我们首先整合GEO和TCGA数据库中骨肉瘤的转录组数据集和临床信息，以评估USP22在骨肉瘤中的表达和预后价值。然后，进行差异表达分析和加权基因共表达网络分析（WGCNA）来鉴定USP22相关的共表达基因。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析来探索USP22共表达基因的生物学功能和信号通路。为了验证生物信息学分析的准确性，我们使用siRNA下调骨肉瘤细胞系Sao-2中USP22的表达，并评估其对细胞增殖、迁移、侵袭、凋亡以及关键信号通路调节的影响。我们发现USP22在骨肉瘤细胞系Sao-2中高表达。骨肉瘤组织与骨肉瘤患者不良预后相关。 USP22 还显示出作为骨肉瘤诊断标记物的潜力。此外，还鉴定出344个USP22相关共表达基因，主要涉及糖酵解、氧化磷酸化、剪接体、产热和细胞周期等信号通路。体外实验证实了生物信息学分析的准确性和可靠性。我们发现USP22的下调可以抑制Sao-2细胞的增殖、迁移、侵袭并诱导细胞凋亡。此外，USP22的下调显着降低了Sao-2细胞的有氧糖酵解水平，并抑制了有氧糖酵解途径中关键酶和转运蛋白的表达，如HK2、PKM2和GLUT1。USP22在该病的发生、发展和预后中发挥着关键作用骨肉瘤。 USP22可以通过调节糖酵解途径影响Sao-2细胞的增殖、凋亡、迁移和侵袭，从而促进骨肉瘤进展。因此，USP22可能是治疗骨肉瘤的潜在治疗靶点。©2024Zhang等人。

Osteosarcoma is the most common primary malignant bone tumor, but its pathogenesis remains unclear. Ubiquitin-specific processing peptidase 22 (USP22) is reported to be highly expressed and associated with tumor malignancy and prognosis in cancers. However, the role and mechanism of USP22 in osteosarcoma is not fully understood. This study aims to investigate the function and potential mechanism of USP22 in osteosarcoma using bioinformatics analysis combined with experimental validation.We first integrated transcriptomic datasets and clinical information of osteosarcoma from GEO and TCGA databases to assess the expression and prognostic value of USP22 in osteosarcoma. Then, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify USP22-related co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways of USP22 co-expressed genes. To validate the accuracy of bioinformatics analyses, we downregulated USP22 expression in osteosarcoma cell line Sao-2 using siRNA and assessed its effect on cell proliferation, migration, invasion, apoptosis, and regulation of key signaling pathways.We found that USP22 was highly expressed in osteosarcoma tissues and correlated with poor prognosis in osteosarcoma patients. USP22 also showed potential as a diagnostic marker for osteosarcoma. In addition, 344 USP22-related co-expressed genes were identified, mainly involved in signaling pathways such as glycolysis, oxidative phosphorylation, spliceosome, thermogenesis, and cell cycle. The in vitro experiments confirmed the accuracy and reliability of bioinformatics analyses. We found that downregulation of USP22 could inhibit Sao-2 cell proliferation, migration, invasion, and induce apoptosis. Furthermore, downregulation of USP22 significantly reduced aerobic glycolysis levels in Sao-2 cells and inhibited the expression of key enzymes and transporters in aerobic glycolysis pathways such as HK2, PKM2, and GLUT1.USP22 plays a critical role in the occurrence, development, and prognosis of osteosarcoma. USP22 could influence Sao-2 cell proliferation, apoptosis, migration, and invasion by regulating the glycolysis pathway, thereby promoting osteosarcoma progression. Therefore, USP22 may be a potential therapeutic target for the treatment of osteosarcoma.© 2024 Zhang et al.