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. 2021 Jan 7;22(2):543.
doi: 10.3390/ijms22020543.

mRNA and miRNA Expression Analyses of the MYC/ E2F/miR-17-92 Network in the Most Common Pediatric Brain Tumors

Renata Gruszka  1   2 , Krzysztof Zakrzewski  3 , Paweł Piotr Liberski  1 , Magdalena Zakrzewska  1
Affiliations

mRNA and miRNA Expression Analyses of the MYC/ E2F/miR-17-92 Network in the Most Common Pediatric Brain Tumors

Renata Gruszka et al. Int J Mol Sci. .

Abstract

Numerous molecular factors disrupt the correctness of the cell cycle process leading to the development of cancer due to increased cell proliferation. Among known causative factors of such process is abnormal gene expression. Nowadays in the light of current knowledge such alterations are frequently considered in the context of mRNA-miRNA correlation. One of the molecular factors with potential value in tumorigenesis is the feedback loop between MYC and E2F genes in which miR-17-5p and miR-20a from the miR-17-92 cluster are involved. The current literature shows that overexpression of the members of the OncomiR-1 are involved in the development of many solid tumors. In the present work, we investigated the expression of components of the MYC/E2F/miR-17-92 network and their closely related elements including members of MYC and E2F families and miRNAs from two paralogs of miR-17-92: miR-106b-25 and miR-106a-363, in the most common brain tumors of childhood, pilocytic astrocytoma (PA), WHO grade 1; ependymoma (EP), WHO grade 2; and medulloblastoma (MB), WHO grade 4. We showed that the highest gene expression was observed in the MYC family for MYCN and in the E2F family for E2F2. Positive correlation was observed between the gene expression and tumor grade and type, with the highest expression being noted for medulloblastomas, followed by ependymomas, and the lowest for pilocytic astrocytomas. Most members of miR-17-92, miR-106a-363 and miR-106b-25 clusters were upregulated and the highest expression was noted for miR-18a and miR-18b. The rest of the miRNAs, including miR-19a, miR-92a, miR-106a, miR-93, or miR-25 also showed high values. miR-17-5p, miR-20a obtained a high level of expression in medulloblastomas and ependymomas, while close to the control in the pilocytic astrocytoma samples. miRNA expression also depended on tumor grade and histology.

Keywords: OncomiR-1; brain tumor; ependymoma; medulloblastoma; miR-106a-363; miR-106b-25; miR-17-92; microRNA; pilocytic astrocytoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Expression of genes from the MYC and E2F families in three groups of pediatric brain tumors: medulloblastomas, ependymomas, and pilocytic astrocytomas. (A) Relative expression of MYCC, MYCN, MYCL, E2F1, F2F2, and E2F3 genes given in ddCt values. (B) Relative expression of MYCC, MYCN, MYCL, E2F1, F2F2, and E2F3 with an indication of the differences in expression between the groups studied; * p < 0.05, *** p < 0.001.
Figure 2
Figure 2
Relative expression level of members of three paralogical clusters in medulloblastoma, ependymoma, and pilocytic astrocytoma. (A) miR-17-92 cluster; (B) miR-106a-363 cluster; (C) miR-106b-25 cluster. Relative expression is given in ddCt value.
Figure 3
Figure 3
Relative expression of miRNAs from miR-17-92, miR-106a-363, and miR-106b-25 clusters in the analyzed groups of pediatric brain tumors. Relative expression is given in ddCt values. (A) miR-17-92 cluster; (B) miR-106a-363 cluster; (C) miR-106b-25 cluster; * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 3
Figure 3
Relative expression of miRNAs from miR-17-92, miR-106a-363, and miR-106b-25 clusters in the analyzed groups of pediatric brain tumors. Relative expression is given in ddCt values. (A) miR-17-92 cluster; (B) miR-106a-363 cluster; (C) miR-106b-25 cluster; * p < 0.05, ** p < 0.01, *** p < 0.001.
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