LncRNA LINC00689 promotes the growth, metastasis and glycolysis of glioma cells by targeting miR-338-3p/PKM2 axis
LncRNA LINC00689 promotes the growth, metastasis and glycolysis of glioma cells by targeting miR-338-3p/PKM2 axis
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LncRNA LINC00689通过靶向miR-338-3p/PKM2轴促进胶质瘤细胞的生长、转移和糖酵解
DOI：
10.1016/j.biopha.2019.109069
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发表时间：
2019-09-01
影响因子：
7.5
通讯作者：
Xu, Qiuran
中科院分区：
文献类型：
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作者：
Liu, Xin;Zhu, Qiaojuan;Xu, Qiuran
越来越多的证据表明，长非编码RNA(LncRNAs)与胶质瘤的发生、发展密切相关。最近的研究发现，LINC00689(LINC00689)与肥胖相关，并参与真核基因的表达。然而，LINC00689是否在胶质瘤进展中起关键作用仍不清楚。在这里，我们基于GSE数据集(GSE4290)发现了一个在胶质瘤中与正常脑组织相比高表达的lncRNA LINC00689。我们的数据分析表明，LINC00689在胶质瘤组织和细胞系中的表达上调。LINC00689的高表达与肿瘤大小<3 cm、肿瘤分级高、KPS评分低、预后差密切相关。进一步研究表明，LINC00689基因敲除对胶质瘤细胞的增殖、迁移、侵袭和糖酵解有明显的抑制作用。此外，沉默LINC00689显著抑制了体内胶质瘤细胞的生长。从机制上讲，LINC00689通过直接与miR-338-3p相互作用，促进丙酮酸激酶M2(PKM2)的表达，从而发挥竞争内源性RNA(CerNA)的作用。值得注意的是，我们还发现，PKM2的修复取消了LINC00689沉默对胶质瘤细胞增殖、迁移、侵袭和糖酵解的影响。综上所述，我们的结果提示LINC00689/miR-338-3p/PKM2轴可能在脑胶质瘤的发生发展中起重要作用。
Accumulating evidence supports that long non-coding RNAs (lncRNAs) are implicated in the tumorigenesis and progression of glioma. Recent studies find that lncRNA long intergenic non-protein coding RNA 689 (LINC00689) is associated with obesity and participates in eukaryotic gene expression. However, whether LINC00689 plays a critical role in glioma progression remains unknown. Here, we identified a highly expressed lncRNA LINC00689 in gliomas compared to normal brain tissues based on the GSE dataset (GSE4290). The analysis of our data indicated that the expression of LINC00689 was up-regulated in glioma tissues and cell lines. Moreover, the high expression of LINC00689 was closely correlated with tumor size >= 3 cm, high tumor grade, low KPS scores and poor prognosis of glioma patients. Further investigation demonstrated that LINC00689 knockdown markedly repressed the proliferation, migration, invasion and glycolysis of glioma cells. Additionally, silencing of LINC00689 significantly suppressed the growth of glioma cells in vivo. Mechanistically, LINC00689 functioned as a competing endogenous RNA (ceRNA) by directly interacting with miR-338-3p to promote pyruvate kinase M2 (PKM2) expression. Notably, we also revealed that restoration of PKM2 abolished the effects of LINC00689 silencing on glioma cell proliferation, migration, invasion and glycolysis. In summary, our results suggested that LINC00689/miR-338-3p/PKM2 axis might play an essential role in glioma progression.