You Xue, Wang Minghe, Wang Xuejing, Wang Xiaotong, Cheng Yuting, Zhang Chuan, Miao Qingrun, Feng Ying
Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, 133 Hehua Road, Jining, Shandong, 272067, PR China.
College of Second Clinical Medical, Jining Medical University, Jining, Shandong, 272067, PR China.
Heliyon. 2024 Sep 19;10(18):e38153. doi: 10.1016/j.heliyon.2024.e38153. eCollection 2024 Sep 30.
Gastric cancer (GC) is a prevalent global malignancy, often diagnosed at advanced stage due to a lack of early symptoms and reliable markers. Previous research has identified gliomedin (GLDN) as a potential predictive marker for poor prognosis in cancer patients. However, the specific relationship between GLDN expression and GC prognosis has been unclear. Using the Tumor-Immune System Interaction Database (TISIDB), we examined GLDN expression in GC tissues and found a positive correlation with advanced clinical stages. Kaplan-Meier Plotter analysis further demonstrated that elevated GLDN levels were closely associated with poor prognosis in GC patients. To explore the functional significance of GLDN in GC, we conducted experiments involving GLDN overexpression and knockdown in GC cell lines, as well as subcutaneous tumor formation in nude mice. Our findings provided compelling evidence that GLDN promotes GC cell proliferation, viability, and migration, significantly enhancing tumor growth in vivo. Mechanistically, RNA-sequencing (RNA-seq) combined with bioinformatics analysis revealed that GLDN influences genes enriched in the p53 signaling pathway. Our data suggest that GLDN likely regulates cell proliferation through the p53-p21-CyclinD/CDK4 signaling axis. In conclusion, our study underscores GLDN's critical role in regulating GC cell proliferation and migration, and proposes its potential as a prognostic marker for GC patients.
胃癌(GC)是一种全球普遍存在的恶性肿瘤,由于缺乏早期症状和可靠的标志物,通常在晚期才被诊断出来。先前的研究已将神经胶质瘤调节蛋白(GLDN)确定为癌症患者预后不良的潜在预测标志物。然而,GLDN表达与GC预后之间的具体关系尚不清楚。我们使用肿瘤-免疫系统相互作用数据库(TISIDB)检测了GC组织中GLDN的表达,发现其与晚期临床分期呈正相关。Kaplan-Meier Plotter分析进一步表明,GC患者中GLDN水平升高与预后不良密切相关。为了探究GLDN在GC中的功能意义,我们在GC细胞系中进行了GLDN过表达和敲低实验,以及在裸鼠体内进行皮下肿瘤形成实验。我们的研究结果提供了有力证据,表明GLDN促进GC细胞增殖、活力和迁移,显著增强体内肿瘤生长。从机制上讲,RNA测序(RNA-seq)结合生物信息学分析表明,GLDN影响富含p53信号通路的基因。我们的数据表明,GLDN可能通过p53-p2l-CyclinD/CDK4信号轴调节细胞增殖。总之,我们的研究强调了GLDN在调节GC细胞增殖和迁移中的关键作用,并提出了其作为GC患者预后标志物的潜力。