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儿童脑肿瘤中 miRNA 靶基因网络的鉴定和验证。

Identification and validation of miRNA-target genes network in pediatric brain tumors.

机构信息

Faculty of Biology and Environmental Protection, Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland.

Faculty of Medicine, Medical University of Lodz, ul. Aleja T. Kosciuszki 4, 90-419, Lodz, Poland.

出版信息

Sci Rep. 2024 Aug 2;14(1):17922. doi: 10.1038/s41598-024-68945-z.

Abstract

Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.

摘要

miRNA 水平的改变在各种类型的癌症中都有观察到,影响了许多细胞过程,并增加了它们在联合治疗中的潜在用途,包括脑肿瘤。最近对脑肿瘤遗传学和表观遗传学的理解的进展表明了新的异常和关联,因此不断更新知识和分类至关重要。在这里,我们对 123 例儿童脑肿瘤(毛细胞星形细胞瘤、髓母细胞瘤、室管膜瘤)样本进行了分子分析,重点是鉴定可能受关键致癌 miRNA-1:miR-17-5p 和 miR-20a-5p 调节的基因。基于微阵列基因表达分析和 qRT-PCR 分析,我们选择了六个(WEE1、CCND1、VEGFA、PTPRO、TP53INP1、BCL2L11)最有前途的靶基因进行进一步实验。WEE1、CCND1、PTPRO、TP53INP1 基因在所有测试实体中的表达水平均升高,与室管膜瘤和髓母细胞瘤相比,在毛细胞星形细胞瘤中增加的最低。研究结果表明基因表达与 WHO 分级和亚型之间存在相关性。此外,我们的分析表明,现在基因组和表观遗传途径的整合应该为进一步的分子研究指明方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17b7/11297236/378145a8cf9c/41598_2024_68945_Fig1_HTML.jpg

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