A microRNA profile of pediatric glioblastoma: The role of NUCKS1 upregulation

Abstract

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 (NUCKS1) 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.

Keywords: gene; glioblastoma multiforme; high-grade glioma; microRNAs; pediatric brain tumor.

Figure 1.

Heatmap of microRNA expression across tumors (GBM1, GBM2 and GBM3) and the non-tumoral control. The color key describes the color associated with each level of expression (0–40 indicates the normalized Cq values). The heatmap was generated using R software v3.5.1 and the ‘HTqPCR’ package. GBM, glioblastoma multiforme; POOL, non-tumoral pool group.

Figure 2.

Expression of NUCKS1 in GBMs (GBM1-3) and GBM cell lines (A172, U87MG and resistant-T98G cells). *P<0.05 in the T98G vs. the GBM1, GBM2, GBM3, U87MG and A172 cell lines. GBM, glioblastoma multiforme; NUCKS1, nuclear casein kinase and cyclin dependent kinase substrate 1; POOL, non-tumoral pool group.