Giunti Laura, Da Ros Martina, De Gregorio Veronica, Magi Alberto, Landini Samuela, Mazzinghi Benedetta, Buccoliero Anna Maria, Genitori Lorenzo, Giglio Sabrina, Sardi Iacopo
Medical Genetics Unit, Meyer Children's University Hospital, I-50139 Florence, Italy.
Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children's University Hospital, I-50139 Florence, Italy.
Mol Clin Oncol. 2019 Mar;10(3):331-338. doi: 10.3892/mco.2019.1795. Epub 2019 Jan 2.
MicroRNAs (miRNAs/miRs) are a novel class of gene regulators that may be involved in tumor chemoresistance. Recently, specific miRNA expression profiles have been identified in adult glioblastoma (aGBM), but there are only limited data available on the role of miRNAs in pediatric GBM (pGBM). In the present study, the expression profile of miRNAs was examined in seven pGBMs and three human GBM cell lines (U87MG, A172 and T98G), compared with a non-tumoral pool of pediatric cerebral cortex samples by microarray analysis. A set of differentially expressed miRNAs was identified, including miR-490, miR-876-3p, miR-876-5p, miR-448 and miR-137 (downregulated), as well as miR-501-3p (upregulated). Through bioinformatics analysis, a series of target genes was predicted. In addition, similar gene expression patterns in pGBMs and cell lines was confirmed. Of note, drug resistant T98G cells had upregulated nuclear casein kinase and cyclin-dependent kinase substrate 1 () expression, a protein overexpressed in many tumors that serves an important role in cell proliferation and progression. On the basis of the present preliminary report, it could be intriguing to further investigate the relationship between each of the identified differentially expressed miRNAs and NUCKS1, in order to clarify their involvement in the multi-drug resistance mechanism of pGBMs.
微小RNA（miRNA/miR）是一类新型的基因调节因子，可能参与肿瘤化疗耐药。最近，已在成人胶质母细胞瘤（aGBM）中鉴定出特定的miRNA表达谱，但关于miRNA在儿童胶质母细胞瘤（pGBM）中的作用仅有有限的数据。在本研究中，通过微阵列分析，检测了7例pGBM和3种人胶质母细胞瘤细胞系（U87MG、A172和T98G）中miRNA的表达谱，并与一组小儿大脑皮质非肿瘤样本进行比较。鉴定出一组差异表达的miRNA，包括miR-490、miR-876-3p、miR-876-5p、miR-448和miR-137（下调），以及miR-501-3p（上调）。通过生物信息学分析，预测了一系列靶基因。此外，还证实了pGBM和细胞系中存在相似的基因表达模式。值得注意的是，耐药性T98G细胞中核酪蛋白激酶和细胞周期蛋白依赖性激酶底物1（NUCKS1）的表达上调，该蛋白在许多肿瘤中过表达，在细胞增殖和进展中起重要作用。基于本初步报告，进一步研究每种已鉴定的差异表达miRNA与NUCKS1之间的关系，以阐明它们在pGBM多药耐药机制中的作用，可能会很有趣。
