Department of Orthopedic Surgery, Shandong Provincial Third Hospital, Jinan, 250031, Shandong, China.
Department of Orthopedic Surgery, Taishan Hospital of Shandong Province, Tai'an, 271000, Shandong, China.
Biochem Biophys Res Commun. 2020 Mar 12;523(3):766-772. doi: 10.1016/j.bbrc.2020.01.016. Epub 2020 Jan 14.
Long noncoding RNA small nucleolus RNA host gene 14 (SNHG14) has been shown to exert oncogenic functions in seceral cancers, but its role in osteosarcoma still unclear. In this present study, we found that SNHG14 was significantly upregulated in osteosarcoma tissues and cell lines. Knockdown SNHG14 expression significantly inhibited osteosarcoma cell proliferation through inducing apoptosis. Further functional assays revealed that SNHG14 knockdown dramatically suppressed cell migration and invasion. Bioinformatics analysis and luciferase assays identified that microRNA-433-3p (miR-433-3p) was a direct target of SNHG14, and directly targeted F-box only protein 22 (FBXO22). Mechanistic analysis demonstrated that SNHG14 acted as a ceRNA in modulating osteosarcoma proliferation, migration and invasion by decoying miR-433-3p to upregulate FBXO22 expression. We also observed that knockdown of FBXO22 and SNHG14 and overexpression of miR-433-3p both dramatically suppressed osteosarcoma cell proliferation, migration and invasion, but induced cell apoptosis. Moreover, the suppresive effect of SNHG14 knockdown on osteosarcoma cell proliferation, invasion and migration was attenuated by miR-433-3p inhibitor. Our findings demonstrated that SNHG14 promoted osteosarcoma progression by acting as a ceRNA for miR-433-3p to regulate FBXO22 expression, suggesting that SNHG14 may serve as a potential therapeutic target in osteosarcoma patients.
长链非编码 RNA 小核仁 RNA 宿主基因 14(SNHG14)已被证明在几种癌症中发挥致癌作用,但在骨肉瘤中的作用尚不清楚。在本研究中,我们发现 SNHG14 在骨肉瘤组织和细胞系中显著上调。敲低 SNHG14 表达通过诱导细胞凋亡显著抑制骨肉瘤细胞增殖。进一步的功能测定显示,SNHG14 敲低显著抑制细胞迁移和侵袭。生物信息学分析和荧光素酶报告基因实验鉴定出 microRNA-433-3p(miR-433-3p)是 SNHG14 的直接靶基因,并直接靶向 F-box 仅蛋白 22(FBXO22)。机制分析表明,SNHG14 通过诱饵 miR-433-3p 来上调 FBXO22 表达,从而作为 ceRNA 调节骨肉瘤增殖、迁移和侵袭。我们还观察到,敲低 FBXO22 和 SNHG14 以及过表达 miR-433-3p 均显著抑制骨肉瘤细胞增殖、迁移和侵袭,但诱导细胞凋亡。此外,miR-433-3p 抑制剂减弱了 SNHG14 敲低对骨肉瘤细胞增殖、侵袭和迁移的抑制作用。我们的研究结果表明,SNHG14 通过作为 miR-433-3p 的 ceRNA 来调节 FBXO22 表达促进骨肉瘤进展,表明 SNHG14 可能成为骨肉瘤患者的潜在治疗靶点。