miR-196B-5P and miR-200B-3P Are Differentially Expressed in Medulloblastomas of Adults and Children

Abstract

Medulloblastoma is a highly aggressive brain tumor that typically affects children, while in adults it represents ~1% of all brain tumors. Little is known about microRNA expression profile of the rare adult medulloblastoma. The main aim of this study was to identify peculiar differences in microRNA expression between childhood and adult medulloblastoma. Medulloblastomas were profiled for microRNA expression using the Exiqon Human miRNome panel (I + II) analyzing 752 microRNAs in a training set of six adult and six childhood cases. Then, the most differentially expressed microRNAs were validated in a total of 21 adult and 19 childhood cases. Eight microRNAs (miR-196b-5p, miR-183-5p, miR-200b-3p, miR-196a-5p, miR-193a-3p, miR-29c-3p, miR-33b-5p, and miR-200a-3p) were differentially expressed in medulloblastoma of adults and children. Analysis of the validation set confirmed that miR-196b-5p and miR-200b-3p were significantly overexpressed in medulloblastoma of adults as compared with those of children. We followed an in silico approach to investigate direct targets and the pathways involved for the two microRNAs (miR-196b and miR-200b) differently expressed between adult and childhood medulloblastoma. Adult and childhood medulloblastoma have different miRNA expression profiles. In particular, the differential dysregulation of miR-196b-5p and miR-200b-3p characterizes the miRNA profile of adult medulloblastoma and suggests potential targets for novel diagnostic, prognostic, or therapeutic strategies.

Keywords: adult medulloblastoma; childhood medulloblastoma; microRNA; microRNA profile.

Figure 1

Classification of medulloblastoma by immunohistochemical staining. Cases were classified into WNT subgroup (nuclear β-catenin, positive; GAB1, negative; and YAP1, positive), SHH subgroup (nuclear β-catenin, negative; GAB1, positive; YAP1, positive; and filamin A, positive), and non-SHH/WNT subgroup (nuclear β-catenin, negative; YAP1, negative; and filamin A, negative). Representative pictures (40×) of each subgroup are shown.

Figure 2

Histopathological distribution in adult and children molecular subgroups. Each column shows the number of cases in each category.

Figure 3

Differential miRNAs expression in the adult MB group versus the childhood MB group after validation test. ** p < 0.01 and *** p < 0.001.

Figure 4

Boxplot of miRNAs expression in molecular subgroups of adult medulloblastoma. Log2(FC) was calculated on CH group. * p < 0.05.

Figure 5

Protein–protein interaction (PPI) network for miR-196b-5p targets. (A) Proteins in the network are represented as colored points (“nodes”), a colored link represents each protein interaction (pink if experimental evidence, light green if text mining evidence, or light blue if database evidence, see Material and Methods section). Red ellipses highlight dense clusters; (B) The top ten nodes with a high degree in PPI of miR-196b-5p targets are represented in red, orange, or yellow boxes. The numbers inside the boxes represent the number of protein connections (degree) of each node.

Figure 6

PPI network for miR-200b-3p targets. (A) Proteins in the network are represented as colored points (“nodes”), a colored link represents each protein interaction (pink if experimental evidence, light green if text mining evidence, or light blue if database evidence, see Material and Methods section); (B) The top ten nodes with a high degree in PPI of miR-200b-3p targets are represented in red, orange, or yellow boxes. The numbers inside the boxes represent the number of protein connections (degree) of each node.