Xia Xiaochao, Wang Zihao, Song Lvmeng, Cheng Yinchuan, Xiong Ping, Li Shun
Departments of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Cancer Med. 2024 Dec;13(23):e70412. doi: 10.1002/cam4.70412.
Previous studies have implicated the involvement of FAM3C in cancerous development and progression. Herein, we aimed to further investigate the oncological mechanism of FAM3C, specifically in glioma.
We utilized open-source bioinformatics tools and platforms to analyze the transcriptional expression levels, prognosis, and correlation with clinical variables of FAM3C in gliomas, and subsequently, to hypothesize its potential molecular functions and possibly associated signaling pathways. Following this, glioma tissues were obtained from resected specimens of patients to assess the expression of FAM3C and molecular markers related to epithelial-mesenchymal transition (EMT) and Notch signaling pathways. Furthermore, glioma cell lines were subjected to treatments including FAM3C siRNA knockdown, lentiviral overexpression, and Notch signaling pathway blockade, enabling the investigation of molecular functions of FAM3C in vitro, particularly in EMT and Notch signaling pathways, as well as its effects on cancer cell proliferation, cell cycle progression, apoptosis, and invasion, using assays such as MMT cell proliferation assay, transwell migration, and flow cytometry analysis. Finally, a mouse subcutaneous xenograft model was established to explore the integrative function of FAM3C in glioma growth in vivo.
The expression level of FAM3C correlated with the progression of glioma grade and served as a prognostic indicator for poor patient outcomes. Subsequent experiments conducted on glioma cell lines, tumor tissues, and mouse models reinforced the close association of FAM3C with processes including glioma cell proliferation, cell cycle progression, apoptosis, and invasion. Additionally, it was observed that FAM3C is involved in the regulation of the Notch signaling pathway.
FAM3C emerges as a potential candidate for clinical detection and prognostic biomarker application. Its regulatory role in glioma cell proliferation, cell cycle progression, and modulation of epithelial-mesenchymal transition-driven invasion and migration via the Notch signaling pathway implies its potential to unveil novel therapeutic targets for glioma treatment.
先前的研究表明FAM3C参与癌症的发生和发展。在此，我们旨在进一步研究FAM3C的肿瘤发生机制，特别是在胶质瘤中的机制。
我们利用开源生物信息学工具和平台分析FAM3C在胶质瘤中的转录表达水平、预后以及与临床变量的相关性，随后推测其潜在的分子功能和可能相关的信号通路。在此之后，从患者的切除标本中获取胶质瘤组织，以评估FAM3C以及与上皮-间质转化（EMT）和Notch信号通路相关的分子标志物的表达。此外，对胶质瘤细胞系进行包括FAM3C siRNA敲低、慢病毒过表达和Notch信号通路阻断在内的处理，通过MMT细胞增殖试验、Transwell迁移试验和流式细胞术分析等实验，研究FAM3C在体外的分子功能，特别是在EMT和Notch信号通路中的功能，以及其对癌细胞增殖、细胞周期进程、凋亡和侵袭的影响。最后，建立小鼠皮下异种移植模型，以探索FAM3C在体内胶质瘤生长中的综合功能。
FAM3C的表达水平与胶质瘤分级的进展相关，并可作为患者预后不良的预测指标。随后在胶质瘤细胞系、肿瘤组织和小鼠模型上进行的实验进一步证实了FAM3C与胶质瘤细胞增殖、细胞周期进程、凋亡和侵袭等过程密切相关。此外，还观察到FAM3C参与Notch信号通路的调控。
FAM3C有望成为临床检测和预后生物标志物应用的潜在候选者。它在胶质瘤细胞增殖、细胞周期进程以及通过Notch信号通路调节上皮-间质转化驱动的侵袭和迁移中的调节作用，意味着它有可能揭示胶质瘤治疗的新靶点。
