Long noncoding RNA NR2F1-AS1 enhances the malignant properties of osteosarcoma by increasing forkhead box A1 expression via sponging of microRNA-483-3p
Long noncoding RNA NR2F1-AS1 enhances the malignant properties of osteosarcoma by increasing forkhead box A1 expression via sponging of microRNA-483-3p
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DOI：
10.18632/aging.102563
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发表时间：
2019-12-15
期刊：
影响因子：
5.2
通讯作者：
Zhang, Xiaojing
中科院分区：
文献类型：
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作者：
Li, Shenglong;Zheng, Ke;Zhang, Xiaojing
长链非编码RNA NR2F1-AS1被发现可促进肝细胞癌和子宫内膜癌的发展。在本研究中，我们测量了骨肉瘤（OS）中NR2F1-AS1的表达，确定了NR2F1-AS1在OS恶性特性中的参与，并研究了其潜在机制。发现 NR2F1-AS1 在 OS 肿瘤和细胞系中表达上调。 NR2F1-AS1水平升高与OS患者的晚期临床分期和远处转移密切相关。 NR2F1-AS1 高表达组的 OS 患者的总生存期明显短于 NR2F1-AS1 低表达组的患者。 NR2F1-AS1 敲低可抑制 OS 细胞增殖、迁移和侵袭，并在体外促进细胞周期停滞和凋亡，并在体内减缓肿瘤生长。研究发现 NR2F1-AS1 通过直接海绵化 microRNA-483-3p (miR-483-3p) 并上调其靶标癌基因叉头盒 Al (FOXA1) 来发挥竞争性内源 RNA 的作用。最后，拯救实验表明，miR-483-3p 的敲低和 FOXA1 表达的恢复均减弱了 NR2F1-AS1 敲低对 OS 细胞的影响。因此，NR2F1-AS1 通过海绵 miR-483-3p 从而上调 FOXA1 在 OS 中发挥致癌作用，这表明骨肉瘤治疗的另一个靶点。
The long noncoding RNA NR2F1-AS1 has been found to promote the development of hepatocellular carcinoma and endometrial cancer. In this study, we measured NR2F1-AS1 expression in osteosarcoma (OS), determined the involvement of NR2F1-AS1 in the malignant properties of OS, and investigated the underlying mechanisms. NR2F1-AS1 was found to be upregulated in OS tumors and cell lines. The increased NR2F1-AS1 level was closely associated with advanced clinical stage and distant metastasis in patients with OS. Patients with OS in an NR2F1-AS1 high-expression group demonstrated significantly shorter overall survival than did patients in an NR2F1-AS1 low-expression group. NR2F1-AS1 knockdown inhibited OS cell proliferation, migration, and invasion and promoted cell cycle arrest and apoptosis in vitro and slowed tumor growth in vivo. NR2F1-AS1 was found to function as a competing endogenous RNA by directly sponging microRNA-483-3p (miR-483-3p) and upregulating its target oncogene forkhead box Al (FOXA1). Finally, rescue experiments revealed that knockdown of miR-483-3p and recovery of FOXA1 expression both attenuated the influence of the NR2F1-AS1 knockdown on OS cells. Thus, NR2F1-AS1 plays an oncogenic role in OS through sponging miR-483-3p and thereby upregulating FOXA1, suggesting an additional target for osteosarcoma therapeutics.