多形性胶质母细胞瘤（GBM）是一种高度侵袭性的脑肿瘤，预后较差。裂解因子 Im 25 (CFIm25) 是 CFIm 复合物的重要组成部分，在调节 mRNA 3'-UTR 长度方面发挥着关键作用，并与包括 GBM 在内的多种癌症有关。本研究旨在探讨特定 microRNA (miRNA) 对 GBM（一种高度侵袭性脑肿瘤）中 CFIm25 表达的调节影响。生物信息学分析确定了针对 CFIm25 mRNA 的 miRNA 候选者，并使用 NCBI 数据库 (GSE90603) 中的基因表达谱进行进一步分析。使用 qRT-PCR 评估 GBM 临床样本 (n = 20) 和非恶性脑组织 (n = 5) 中 CFIm25 和选定 miRNA 的表达水平。此外，还进行了 MTT 测定来检查 miRNA 过表达对 U251 细胞活力的影响。使用表达已鉴定的 miRNA 的慢病毒载体在 U251 细胞系中通过实验验证其对 CFIm25 的调节作用，并进行蛋白质印迹分析以确定 CFIm25 蛋白水平。我们观察到，与非恶性脑组织相比，GBM 样本中 miR-23、miR-24 和 miR-27 表达水平显着升高，且 CFIm25 表达显着降低。特别是，U251细胞中miR-23、miR-24和miR-27的过表达导致CFIm25在mRNA和蛋白质水平上下调，而它们的抑制则增加了CFIm25并减少了细胞增殖。这些观察结果强烈表明 miR-23、miR-24 和 miR-27 参与调节 GBM 中的 CFIm25 表达，强调它们作为增强胶质母细胞瘤治疗反应的有希望的治疗靶点的潜力。© 2024。作者获得独家许可Springer Science Business Media, LLC，隶属于 Springer Nature。

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. The cleavage factor Im 25 (CFIm25), a crucial component of the CFIm complex, plays a key role in regulating the length of the mRNA 3'-UTR and has been implicated in various cancers, including GBM. This study sought to investigate the regulatory influence of specific microRNAs (miRNAs) on CFIm25 expression in GBM, a highly aggressive brain tumor. Bioinformatics analysis identified miRNA candidates targeting CFIm25 mRNA, and gene expression profiles from the NCBI database (GSE90603) were used for further analysis. Expression levels of CFIm25 and selected miRNAs were assessed using qRT-PCR in GBM clinical samples (n = 20) and non-malignant brain tissues (n = 5). Additionally, the MTT assay was performed to examine the effect of miRNA overexpression on U251 cell viability. Lentivectors expressing the identified miRNAs were employed to experimentally validate their regulatory role on CFIm25 in U251 cell lines, and Western blot analysis was conducted to determine CFIm25 protein levels. We observed significantly increased levels of miR-23, miR-24, and miR-27 expression, associated with a marked reduction in CFIm25 expression in GBM samples compared to non-malignant brain tissues. In particular, overexpression of miR-23, miR-24, and miR-27 in U251 cells resulted in CFIm25 downregulation at both the mRNA and protein levels, while their inhibition increased CFIm25 and reduced cell proliferation. These observations strongly implicate miR-23, miR-24, and miR-27 in regulating CFIm25 expression in GBM, emphasizing their potential as promising therapeutic targets for enhancing treatment responses in glioblastoma.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.