Hand and Foot Surgical Center, Provincial Hospital Affiliated to Shandong University, Jinan, 250000, Shangdong, China.
In Vitro Cell Dev Biol Anim. 2019 Oct;55(9):694-702. doi: 10.1007/s11626-019-00386-9. Epub 2019 Aug 7.
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.
骨肉瘤在全球范围内普遍存在，是一种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，发挥致癌或肿瘤抑制功能。然而，KCNQ1OT1 在骨肉瘤中的参与尚未得到详细阐述。在这项研究中，我们专注于研究 KCNQ1OT1 在骨肉瘤中的功能及其潜在机制。我们的工作通过 qRT-PCR 证明了 KCNQ1OT1 在骨肉瘤中的上调。此外，功能丧失实验（CCK-8、transwell 迁移）表明 KCNQ1OT1 促进骨肉瘤细胞的增殖和迁移。机制上，KCNQ1OT1 作为 miR-4458 的海绵体，拮抗其对 CCND2 表达的肿瘤抑制作用。通过 caspase-3 活性测定揭示了 KCNQ1OT1 的抗凋亡性质。过表达的 KCNQ1OT1 作为 miR-4458 的竞争性内源 RNA（ceRNA），进而增强了靶基因 CCND2 的表达。通过挽救实验的结果表明，KCNQ1OT1 的致癌作用是通过在骨肉瘤发展过程中海绵吸附 miR-4458 和上调 CCND2 来实现的，为骨肉瘤治疗提供了新的干预视角。
