Xiao Yun, Zhu Ying, Chen Jiaojiao, Wu Mei, Wang Lan, Su Li, Feng Fei, Hou Yanli
Department of Oncology and Hematology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
Discov Oncol. 2024 Apr 29;15(1):135. doi: 10.1007/s12672-024-00997-z.
Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/β-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.
直肠腺癌（READ）是一种常见的消化道恶性肿瘤。越来越多的研究证实，Ras鸟苷三磷酸酶激活蛋白参与了多种肿瘤的进展。本研究旨在探讨Ras鸟苷三磷酸酶激活蛋白在直肠腺癌中的表达及功能。在本研究中，我们分析了165例直肠腺癌患者和789例正常组织样本的RNA测序数据，鉴定出5603个差异表达基因（DEG），其中包括2937个上调基因和2666个下调基因。此外，在6种Ras鸟苷三磷酸酶激活蛋白中，我们还鉴定出2个失调基因，即RASA4和SYNGAP1。高NF1表达与更长的总生存期相关，而高SYNGAP1表达显示出总生存期延长的趋势。进一步分析揭示了各种癌症样本中Ras鸟苷三磷酸酶激活蛋白的突变频率和拷贝数变异。此外，DNA甲基化分析表明，Ras鸟苷三磷酸酶激活蛋白的DNA甲基化与其表达呈负相关。此外，在Ras鸟苷三磷酸酶激活蛋白中，我们重点研究了SYNGAP1，实验验证证实，SYNGAP1在直肠腺癌中的过表达通过调节Wnt/β-连环蛋白信号通路显著抑制直肠腺癌细胞增殖并增加细胞凋亡。这些发现强调了SYNGAP1在直肠腺癌中的潜在意义，并为进一步的研究和治疗提供了新的见解。
