Osteosarcoma is prevalent worldwide and characterized as a challenging health burden. It has been increasingly indicated that long non-coding RNAs (lncRNAs) are significant in pathological processes of numerous cancers, exerting oncogenic or tumor-suppressive function. However, the participation of KCNQ1OT1 in osteosarcoma has not been elaborated. In this study, we focus on interrogating the function of KCNQ1OT1 and its underlying mechanism in osteosarcoma. Our work demonstrated the upregulation of KCNQ1OT1 in osteosarcoma through qRT-PCR. Besides, loss of function assay (CCK-8, transwell migration) indicated KCNQ1OT1 promoted cell proliferation, migration in osteosarcoma. Mechanically, KCNQ1OT1 acting as sponge for miR-4458 antagonized its tumor-suppressive impact on CCND2 expression. The anti-apoptotic nature of KCNQ1OT1 was also unveiled via caspase-3 activity assay. Overexpressed KCNQ1OT1 acted as competing endogenous RNA (ceRNA) for miR-4458 and subsequently reinforced target gene CCND2. Collectively, the results of rescue experiments suggested that the oncogenic role of KCNQ1OT1 was performed through sponging miR-4458 and upregulating CCND2 during osteosarcoma development, providing a novel perspective of intervention in osteosarcoma management.

中文翻译：

---

LncRNA KCNQ1OT1充当miR-4458的ceRNA，可通过调节CCND2表达来增强骨肉瘤的进展。

骨肉瘤在世界范围内普遍存在，并具有挑战性的健康负担。越来越多的研究表明，长链非编码RNA（lncRNA）在许多癌症的病理过程中具有重要作用，发挥着致癌或抑制肿瘤的功能。但是，KCNQ1OT1在骨肉瘤中的参与尚未阐明。在这项研究中，我们专注于询问KCNQ1OT1的功能及其在骨肉瘤中的潜在机制。我们的工作通过qRT-PCR证明了骨肉瘤中KCNQ1OT1的上调。此外，功能丧失试验（CCK-8，transwell迁移）表明KCNQ1OT1促进了骨肉瘤中的细胞增殖和迁移。机械上，KCNQ1OT1充当miR-4458的海绵，拮抗了其对CCND2表达的肿瘤抑制作用。还通过caspase-3活性测定揭示了KCNQ1OT1的抗凋亡性质。过表达的KCNQ1OT1充当miR-4458的竞争内源RNA（ceRNA），随后增强了靶基因CCND2。总的来说，急救实验的结果表明，在骨肉瘤发展过程中通过海绵化miR-4458和上调CCND2来发挥KCNQ1OT1的致癌作用，从而为骨肉瘤的治疗提供了新的视角。