Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Biochem Biophys Res Commun. 2018 Aug 25;502(4):493-500. doi: 10.1016/j.bbrc.2018.05.198. Epub 2018 Jun 5.
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2.
骨肉瘤(OS)是儿童和青少年中最常见的恶性骨肿瘤。lncRNA 已被证实参与多种癌症。本研究旨在探讨 FOXP4-AS1 对骨肉瘤(OS)发展的影响及其潜在机制。通过 qRT-PCR(实时定量聚合酶链反应)检测 60 例 OS 组织和癌旁组织中的 FOXP4-AS1 表达。我们证实 FOXP4-AS1 在 OS 组织中的表达高于癌旁组织。OS 患者的无病生存和总生存与年龄、性别和肿瘤部位无关,但与 FOXP4-AS1 表达、肿瘤大小和肺转移显著相关。在体外实验中,MG63 细胞表达更高的 FOXP4-AS1 水平,而 U2OS 细胞表达较低,选择它们进行后续研究。过表达 FOXP4-AS1 导致增殖、迁移和侵袭增强,G0/G1 期缩短,并抑制细胞周期。在 MG63 细胞中敲低 FOXP4-AS1 则获得相反的结果。此外,RIP 实验表明,FOXP4-AS1 可通过与 LSD1 和 EZH2 结合抑制 LATS1 表达,从而参与 OS 的发生。综上所述,这些结果表明 FOXP4-AS1 在 OS 中过表达,是 OS 预后的独立危险因素。上调的 FOXP4-AS1 促进 OS 细胞的增殖、迁移和细胞周期,但抑制细胞凋亡。此外,FOXP4-AS1 通过与 LSD1 和 EZH2 结合下调 LATS1 参与 OS 的发生和发展。