Long non-coding RNA ZFAS1 sponges miR-486 to promote osteosarcoma cells progression and metastasis in vitro and vivo.
Long non-coding RNA ZFAS1 sponges miR-486 to promote osteosarcoma cells progression and metastasis in vitro and vivo.
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DOI：
10.18632/oncotarget.22032
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发表时间：
2017-11-28
期刊：
影响因子：
--
通讯作者：
Wan CY
中科院分区：
文献类型：
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作者：
Li N;Sun ZH;Fang M;Xin JY;Wan CY
长非编码 RNA (lncRNA) 已被广泛证明参与骨肉瘤肿瘤发生。 ZFAS1是一种新发现的lncRNA，然而，其在骨肉瘤中的作用仍不清楚。本研究利用lncRNA芯片技术筛选骨肉瘤组织中lncRNA的表达谱，并探讨ZFAS1在骨肉瘤中的调控功能。 LncRNA微阵列检测结果显示，lncRNA ZFAS1在3对骨肉瘤和癌旁非肿瘤组织中显着上调，RT-PCR证实了这一点。此外，在53对骨肉瘤患者样本中，ZFAS1表达上调与不良预后密切相关。体外功能丧失实验表明，ZFAS1 敲低可显着抑制增殖，诱导 G0/G1 期周期停滞并增强细胞凋亡。在体内，ZFAS1 敲低抑制了肿瘤生长。生物信息学在线程序预测 ZFAS1 在具有互补结合位点的 3’-UTR 处海绵 miR-486，并使用荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 测定进行了验证。拯救实验证实，miR-486 可以逆转 ZFAS1 在骨肉瘤发生中的功能。总之，我们的结果证明ZFAS1作为miR-486的竞争性内源RNA（ceRNA），并作为骨肉瘤肿瘤发生中的癌基因，并发现了ZFAS1海绵miR-486的功能调节途径。
Long noncoding RNAs (lncRNAs) have been wildly demonstrated to participate in the osteosarcoma tumorigenesis. ZFAS1 is a novel identified lncRNA, however, its role in osteosarcoma is still unclear. In present study, we utilize lncRNA microarray assay to screen the lncRNA expression profile in osteosarcoma tissue, and investigate the regulatory function of ZFAS1 in osteosarcoma. LncRNA microarray assay revealed that lncRNA ZFAS1 was significantly up-regulated in 3 pairs of osteosarcoma and adjacent non-tumor tissue, which was confirmed by RT-PCR. Furthermore, in 53 pairs of osteosarcoma patient samples, the up-regulated expression of ZFAS1 was closely related to poor prognosis. In vitro, loss-of-function experiments showed that ZFAS1 knockdown significantly suppressed the proliferation, induced cycle arrest at G0/G1 phase and enhance apoptosis. In vivo, ZFAS1 knockdown inhibited the tumor growth. Bioinformatics online programs predicted that ZFAS1 sponge miR-486 at 3’-UTR with complementary binding sites, which was validated using luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Rescue experiments confirmed that miR-486 could reverse the functions of ZFAS1 on osteosarcoma genesis. In conclusion, our results demonstrate that ZFAS1 act as competing endogenous RNA (ceRNA) for miR-486, and act as oncogene in osteosarcoma tumorigenesis, and discover the functional regulatory pathway of ZFAS1 sponging miR-486.
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