Osteosarcoma (OS) is the most common primary malignant bone tumor worldwide. Recently, several studies have shown that the long non-coding RNA (lncRNA) CDKN2B-AS1 plays a critical role in several cancers. However, the function and underlying mechanism of CDKN2B-AS1 in OS development remains elusive. In this study, we firstly assessed the expression of CDKN2B-AS1 in OS tissues and cells, showing that CDKN2B-AS1 expression were remarkably upregulated in OS tissues and cells. Moreover, CDKN2B-AS1 knockdown suppressed cell proliferation, migration, and EMT progress in OS. Interestingly, we found and proved that CDKN2B-AS1 could sponge miR-4458 in OS cells. Moreover, MAP3K3 was certified as a downstream target of miR-4458 in OS. Besides, MAP3K3 was negatively regulated by miR-4458 and positively regulated by CDKN2B-AS1. More importantly, overexpression of MAP3K3 could partly counteract the effect of CDKN2B-AS1 suppression on the biological behavior of OS cells. Also, the in vivo experiments further testified that CDKN2B-AS1 accelerated tumor growth in OS. Our results suggested that CDKN2B-AS1 facilitated OS progression by sponging miR-4458 to enhance MAP3K3 expression, which provides a novel insight into improving diagnostic and therapeutic strategies for patients with OS.

中文翻译：

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长的非编码RNA CDKN2B-AS1通过使miR-4458海绵化来增加MAP3K3的表达，从而促进骨肉瘤。

骨肉瘤（OS）是全球最常见的原发性恶性骨肿瘤。最近，一些研究表明，长的非编码RNA（lncRNA）CDKN2B-AS1在几种癌症中起着至关重要的作用。但是，CDKN2B-AS1在OS开发中的功能和基本机制仍然难以捉摸。在这项研究中，我们首先评估了CDKN2B-AS1在OS组织和细胞中的表达，表明CDKN2B-AS1在OS组织和细胞中的表达显着上调。此外，CDKN2B-AS1敲低抑制了OS中的细胞增殖，迁移和EMT进展。有趣的是，我们发现并证明CDKN2B-AS1可以在OS细胞中吸收miR-4458。此外，MAP3K3被证明是OS中miR-4458的下游目标。此外，MAP3K3受到miR-4458的负调控，而受CDKN2B-AS1的正调控。更重要的是，MAP3K3的过表达可以部分抵消CDKN2B-AS1抑制对OS细胞生物学行为的影响。此外，体内实验进一步证明CDKN2B-AS1促进了OS中肿瘤的生长。我们的结果表明，CDKN2B-AS1通过刺激miR-4458增强MAP3K3表达来促进OS进程，这为改善OS患者的诊断和治疗策略提供了新的见识。