胶质瘤是一种常见且常为致命性的脑肿瘤。尽管分子诊断技术已经提高了对该病的理解，但治疗选择仍然有限。本研究旨在研究INTS9在小核RNA（snRNA）处理中的作用，该过程对产生成熟信使RNA（mRNA）至关重要。我们打算利用大规模数据库进行先进的生物信息学分析，并进行功能实验，以阐明其在胶质瘤治疗中的潜在作用。我们从The Cancer Genome Atlas（TCGA）和中国胶质瘤基因组图谱（CGGA）收集了基因组、蛋白质组和全外显子测序数据，用于进行生物信息学分析。然后，我们通过免疫组化验证了INTS9的蛋白表达，并评估了其与P53和KI67蛋白表达的相关性。我们进行了基因集富集分析（GSEA）以确定改变的信号通路，并对经过siINTS9处理的三个细胞系进行了功能实验。然后，我们还通过整合单细胞测序、12个细胞状态预测和CIBERSORT分析来研究肿瘤异质性对INTS9表达的影响。最后，我们还利用胶质瘤纵向分析（GLASS）数据集观察到INTS9的纵向变化。 我们的研究结果显示，在肿瘤组织中，INTS9水平较非肿瘤组分高，与肿瘤分级和增殖指数相关。TP53突变是与上调INTS9最显著相关的因素，其他潜在的贡献因素包括7号染色体增益/10号染色体缺失的联合、TERT启动子突变和肿瘤突变负荷的增加。在GSEA分析中，我们还将INTS9与细胞增殖和炎症信号通路的增强联系起来。下调INTS9影响细胞增殖和细胞周期调节的功能验证过程。在12个细胞状态的背景下，INTS9与肿瘤干细胞和肿瘤增殖干细胞相关。CIBERSORT分析显示，增加的INTS9与巨噬细胞M0和M2增加，但单核细胞减少有关。从纵面上看，我们还注意到在IDH野生型复发期间，INTS9的表达下降。 本研究评估了INTS9蛋白在胶质瘤发展中的作用及其作为治疗靶点的潜力。结果表明，升高的INTS9水平与增加的增殖能力、更高的肿瘤分级和更差的预后有关，可能是由于TP53突变引起的。本研究强调了INTS9作为胶质瘤治疗的有前景的靶点的潜力。 © 2023. BioMed Central Ltd., part of Springer Nature.

Gliomas, a type of brain neoplasm, are prevalent and often fatal. Molecular diagnostics have improved understanding, but treatment options are limited. This study investigates the role of INTS9 in processing small nuclear RNA (snRNA), which is crucial to generating mature messenger RNA (mRNA). We aim to employ advanced bioinformatics analyses with large-scale databases and conduct functional experiments to elucidate its potential role in glioma therapeutics.We collected genomic, proteomic, and Whole-Exon-Sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) for bioinformatic analyses. Then, we validated INTS9 protein expression through immunohistochemistry and assessed its correlation with P53 and KI67 protein expression. Gene Set Enrichment Analysis (GSEA) was performed to identify altered signaling pathways, and functional experiments were conducted on three cell lines treated with siINTS9. Then, we also investigate the impacts of tumor heterogeneity on INTS9 expression by integrating single-cell sequencing, 12-cell state prediction, and CIBERSORT analyses. Finally, we also observed longitudinal changes in INTS9 using the Glioma Longitudinal Analysis (GLASS) dataset.Our findings showed increased INTS9 levels in tumor tissue compared to non-neoplastic components, correlating with high tumor grading and proliferation index. TP53 mutation was the most notable factor associated with upregulated INTS9, along with other potential contributors, such as combined chromosome 7 gain/10 loss, TERT promoter mutation, and increased Tumor Mutational Burden (TMB). In GSEA analyses, we also linked INTS9 with enhanced cell proliferation and inflammation signaling. Downregulating INTS9 impacted cellular proliferation and cell cycle regulation during the function validation. In the context of the 12 cell states, INTS9 correlated with tumor-stem and tumor-proliferative-stem cells. CIBERSORT analyses revealed increased INTS9 associated with increased macrophage M0 and M2 but depletion of monocytes. Longitudinally, we also noticed that the INTS9 expression declined during recurrence in IDH wildtype.This study assessed the role of INTS9 protein in glioma development and its potential as a therapeutic target. Results indicated elevated INTS9 levels were linked to increased proliferation capacity, higher tumor grading, and poorer prognosis, potentially resulting from TP53 mutations. This research highlights the potential of INTS9 as a promising target for glioma treatment.© 2023. BioMed Central Ltd., part of Springer Nature.