Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma
Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma
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沉默 microRNA-708 通过激活神经胶质瘤中的 SPHK2/AKT/β-连环蛋白途径促进细胞生长和上皮间质转化
DOI：
10.1038/s41419-019-1671-5
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发表时间：
2019-06-06
影响因子：
9
通讯作者：
Long, Hao
中科院分区：
文献类型：
--
作者：
Chen, Yan;Deng, Xubin;Long, Hao
异常microRNA-708（miR-708）表达在癌症研究中经常被报道;然而，其在胶质瘤中的作用尚未被详细研究。我们研究了miR-708在胶质瘤中的功能，发现miR-708在胶质瘤组织和细胞系中表达显著下调。miR-708的恢复在体外和体内均抑制胶质瘤细胞的生长和侵袭。使用荧光素酶和蛋白质印迹分析，将癌基因SPHK 2（鞘氨醇激酶2）鉴定为miR-708的下游靶标。miR-708抑制由SPHK 2激活的AKT/β-连环蛋白信号传导。此外，我们发现miR-708被EZH 2（增强子zeste同源物2）诱导的组蛋白H3赖氨酸27三甲基化和启动子甲基化抑制。总之，我们的研究结果表明，miR-708是胶质瘤肿瘤抑制因子，并表明miR-708是胶质瘤患者的潜在治疗靶点。
Aberrant microRNA-708 (miR-708) expression is frequently reported in cancer studies; however, its role in glioma has not been examined in detail. We investigated miR-708 function in glioma and revealed that miR-708 expression was significantly down-regulated in glioma tissues and cell lines. Restoration of miR-708 inhibited glioma cell growth and invasion both in vitro and in vivo. The oncogene SPHK2 (sphingosine kinase 2) was identified as a downstream target of miR-708 using luciferase and western blot assays. miR-708 inhibited AKT/beta-catenin signaling, which is activated by SPHK2. In addition, we revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. In summary, our findings revealed that miR-708 is a glioma tumor suppressor and suggest that miR-708 is a potential therapeutic target for glioma patients.