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

• Main Authors: Renata Gruszka, Krzysztof Zakrzewski, Paweł Piotr Liberski, Magdalena Zakrzewska
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: OncomiR-1; brain tumor; miR-106a-363; miR-106b-25; miR-17-92; microRNA
• Online Access: https://www.mdpi.com/1422-0067/22/2/543
• ISSN: 1661-6596; 1422-0067

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 <i>MYC </i>and <i>E2F</i> 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 <i>MYC</i>/<i>E2F</i>/miR-17-92 network and their closely related elements including members of <i>MYC</i> and <i>E2F</i> 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 <i>MYC</i> family for <i>MYCN</i> and in the <i>E2F</i> family for <i>E2F2</i>. 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.