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泛癌分析确定一种Ras相关GTP酶为癌症的潜在调节因子。

Pan-Cancer Analysis Identifies a Ras-Related GTPase as a Potential Modulator of Cancer.

作者信息

Hsueh Hsiang-Yin, Gumpper-Fedus Kristyn, Poelstra Jelmer W, Pitter Kenneth L, Cruz-Monserrate Zobeida

机构信息

Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.

出版信息

Int J Mol Sci. 2025 May 6;26(9):4419. doi: 10.3390/ijms26094419.

Abstract

Ras signaling regulates many cellular processes in cancer development. While well-known Ras-related oncogenes, such as KRAS, have been extensively explored, the role of other Ras-related genes in cancer remains poorly studied. Dexamethasone-induced Ras-related protein 1 (RASD1), a member of the Ras superfamily, is widely expressed across various tissues and is involved in inhibiting cell growth and inducing apoptosis, suggesting a potential role as a tumor suppressor. Here, we investigated RASD1 expression across multiple tissues and cancers, utilizing data from The Cancer Genome Atlas (TCGA), Human Protein Atlas, and Genotype-Tissue Expression (GTEx) databases. Our analysis revealed a significant downregulation of RASD1 mRNA expression in several cancer types compared to normal tissues, correlating with low levels of promoter methylation. Interestingly, high RASD1 expression correlated with a favorable prognosis in multiple cancers. Immune cell infiltration analysis indicated that elevated RASD1 expression is associated with an increased infiltration of CD4 T cells and myeloid-derived dendritic cells in cancer. Furthermore, the expression of genes exhibiting similar expression patterns as RASD1 suggest that RASD1 may play a role in interleukin-4-mediated apoptosis and could regulate the transcription of the phosphatase and tensin homolog (PTEN) gene. Overall, these findings suggest that RASD1 may modulate immune signaling and tumor suppressive pathways.

摘要

Ras信号传导在癌症发展过程中调节许多细胞过程。虽然诸如KRAS等著名的Ras相关癌基因已被广泛研究,但其他Ras相关基因在癌症中的作用仍研究不足。地塞米松诱导的Ras相关蛋白1(RASD1)是Ras超家族的成员,在各种组织中广泛表达,参与抑制细胞生长和诱导细胞凋亡,提示其作为肿瘤抑制因子的潜在作用。在此,我们利用来自癌症基因组图谱(TCGA)、人类蛋白质图谱和基因型-组织表达(GTEx)数据库的数据,研究了RASD1在多种组织和癌症中的表达情况。我们的分析显示,与正常组织相比,几种癌症类型中RASD1 mRNA表达显著下调,这与启动子甲基化水平较低相关。有趣的是,高RASD1表达与多种癌症的良好预后相关。免疫细胞浸润分析表明,RASD1表达升高与癌症中CD4 T细胞和髓系来源的树突状细胞浸润增加有关。此外,与RASD1表现出相似表达模式的基因的表达表明,RASD1可能在白细胞介素-4介导的细胞凋亡中发挥作用,并可能调节磷酸酶和张力蛋白同源物(PTEN)基因的转录。总体而言,这些发现表明RASD1可能调节免疫信号传导和肿瘤抑制途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd02/12073092/ce9cac7bb7e7/ijms-26-04419-g001.jpg

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