MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma
MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma
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DOI：
10.1007/s11060-019-03113-2
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发表时间：
2019-04-01
影响因子：
3.9
通讯作者：
Kohmura, Eiji
中科院分区：
文献类型：
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作者：
Sakata, Junichi;Sasayama, Takashi;Kohmura, Eiji
研究背景MicroRNAs（miRs）调控着多种生物学过程，如侵袭、血管生成和转移。胶质母细胞瘤（GBM）转移/转移性播散患者的预后非常差，因此，抑制转移/转移性播散已成为GBM治疗的重要策略。MethodsUsing 76 GBM组织，我们检测了23个GBM相关miRs的表达水平，并比较了有转移/转移性播散的GBM和无转移/转移性播散的GBM之间miRs的表达水平。利用生物信息学网站，我们搜索miRs的靶基因。为了分析靶基因的功能，一些生物学试验和生存分析的Kaplan-Meier方法performed.ResultsWe发现，8个miR的GBM转移/转移性播散显着下降。通过生物信息学分析，我们确定斯钙素-1（stanniocalcin-1，STC 1）是针对这些miRs组合的最可能的靶基因。四种miR（miR-29 B、miR-34 a、miR-101和miR-137）在STC 1 mRNA中具有预测性结合位点，并且STC 1的mRNA表达被这些miR的模拟物下调。此外，这些miR的模拟物和通过siRNA敲低STC 1抑制GBM细胞中的侵袭。具有转移/转移性播散的GBM具有比没有转移/转移性播散的GBM显著更高的STC 1水平。结论STC 1可能是GBM中一种新的受多种miR调控的转移/播散促进因子。由于STC 1是一种分泌型糖蛋白，通过自分泌/旁分泌信号发挥作用，抑制STC 1信号可能成为GBM的一种新的治疗策略。
BackgroundMicroRNAs (miRs) regulate many biological processes, such as invasion, angiogenesis, and metastasis. Glioblastoma (GBM) patients with metastasis/metastatic dissemination have a very poor prognosis; therefore, inhibiting metastasis/metastatic dissemination has become an important therapeutic strategy for GBM treatment.MethodsUsing 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastasis/metastatic dissemination and GBMs without metastasis/metastatic dissemination. Using the bioinformatics web site, we searched the target genes of miRs. To analyze the function of target gene, several biological assays and survival analysis by the Kaplan-Meier method were performed.ResultsWe found that eight miRs were significantly decreased in GBM with metastasis/metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene against the combination of these miRs. Four miRs (miR-29B, miR-34a, miR-101, and miR-137) have predictive binding sites in STC1 mRNA, and mRNA expression of STC1 was downregulated by mimics of these miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastasis/metastatic dissemination had significantly higher levels of STC1 than GBM without metastasis/metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level.ConclusionsSTC1 may be a novel metastasis/metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.