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循环微RNA作为小儿星形细胞瘤的生物标志物

Circulating microRNAs as Biomarkers for Pediatric Astrocytomas.

作者信息

López-Aguilar Javier Enrique, Velázquez-Flores Miguel A, Simón-Martínez Luis A, Ávila-Miranda Richard, Rodríguez-Florido Marco A, Ruiz-Esparza Garrido Ruth

机构信息

Departamento de Oncología, Laboratorio de Investigación en Tumores Cerebrales, Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), 06720, Ciudad de México, México.

Laboratorio de Genómica Funcional, Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), 06720, Ciudad de México, México.

出版信息

Arch Med Res. 2017 May;48(4):323-332. doi: 10.1016/j.arcmed.2017.07.002.

Abstract

BACKGROUND AND AIMS

Since MicroRNAs (miRNAs) are potent regulators of gene expression, their expression and function alterations are associated with different types of cancer, including pediatric astrocytoma. Since the secretion of miRNAs by tumors into corporal fluids has made it possible to identify biomarkers in cancer, their deter mination in pediatric astrocytoma is vital. In order to gain insight into the mechanisms controlled by miRNAs in these neoplasms, we tested the expression of miRNAs 130a, 145, 335, 1303, and let-7g-3p by qPCR in tumors and blood serum from pediatric patients with astrocytoma. The data was analyzed with the DIANA-miRPath v3.0 platform.

RESULTS

The data represented expression changes of all mirRNAs tested in both tumors and blood serum, which strongly suggest their use as circulating biomarkers for astrocytic tumors. The bioinformatic analysis -with DIANA-miRPath v3.0- showed the involvement of these miRNAs in extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer, which control many hallmarks of cancer. In fact, the expression of the proteoglycan syndecan 4 (SDC4) and that of its biosynthetic enzymes, Exostosin Glycosyltransferase 1 (EXT1) and Xylosyltransferase 1 (XYLT1), were altered in pediatric astrocytoma.

CONCLUSIONS

Our results highlight the role of microRNAs in the biology of pediatric astrocytoma and demonstrated for the first time the potential use of some circulating microRNAs as non-invasive biomarkers for this type of tumors, particularly miRs 130a, 145, and 335.

摘要

背景与目的

由于微小RNA(miRNA)是基因表达的有效调节因子,其表达和功能改变与包括儿童星形细胞瘤在内的不同类型癌症相关。肿瘤将miRNA分泌到体液中使得在癌症中鉴定生物标志物成为可能,因此在儿童星形细胞瘤中对其进行测定至关重要。为了深入了解miRNA在这些肿瘤中控制的机制,我们通过qPCR检测了儿童星形细胞瘤患者肿瘤组织和血清中miRNA 130a、145、335、1303和let-7g-3p的表达。数据使用DIANA-miRPath v3.0平台进行分析。

结果

数据显示了所有测试的miRNA在肿瘤组织和血清中的表达变化,这强烈表明它们可作为星形细胞肿瘤的循环生物标志物。使用DIANA-miRPath v3.0进行的生物信息学分析表明这些miRNA参与细胞外基质(ECM)-受体相互作用以及癌症中的蛋白聚糖,而这些控制着癌症的许多特征。事实上,蛋白聚糖syndecan 4(SDC4)及其生物合成酶外切糖苷酶1(EXT1)和木糖基转移酶1(XYLT1)在儿童星形细胞瘤中的表达发生了改变。

结论

我们的结果突出了微小RNA在儿童星形细胞瘤生物学中的作用,并首次证明了一些循环微小RNA作为这类肿瘤非侵入性生物标志物的潜在用途,特别是miR 130a、145和335。

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