PDF(Pubmed)
Abstract：
UNASSIGNED: Fibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins.
UNASSIGNED: Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types.
UNASSIGNED: The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3.
UNASSIGNED: FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.
UNASSIGNED: Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types.
UNASSIGNED: The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3.
UNASSIGNED: FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.
摘要：
■纤维白细胞介素（FGA）和NOTCH3在运动诱导的肌肉适应和结肠腺癌（COAD）进展中都至关重要。本研究旨在阐明FGA和NOTCH3在运动引起的横纹肌表型变异和COAD发育中的作用。此外,它试图评估这些蛋白质的预后意义。
■采用基因集变异分析（GSVA）和蛋白质-蛋白质相互作用（PPI）网络分析来鉴定差异表达基因（DEGs）。进行分子对接研究以评估39种化合物与NOTCH3蛋白的结合亲和力。体外试验,包括机动生存能力，基因表达，和细胞凋亡试验，进行评估甘油磷酸肌醇对FGA和NOTCH3表达的影响。此外,拷贝数变异(CNV)，甲基化状态，并对多种癌症类型进行了生存分析。
■在运动诱导的肌肉样本中，NOTCH信号通路持续上调。高NOTCH3表达与COAD患者预后不良相关,细胞外基质组织，免疫浸润，和PI3K-Akt途径的激活。分子对接鉴定了γ-Glu-Trp，γ-谷氨酰酪氨酸,和17-脱氧皮质醇作为NOTCH3的强粘合剂。甘油磷酸肌醇处理调节FGA和NOTCH3表达，影响细胞增殖和凋亡。CNV和甲基化分析揭示了20种癌症类型中FGA和NOTCH3的特定变化。生存分析显示FGA/NOTCH3表达与生存指标之间有很强的关联，FGA负相关，NOTCH3正相关。
■FGA和NOTCH3在运动诱导的肌肉适应和结肠癌进展中起重要作用。这些蛋白质的表达谱和相互作用提供了有希望的预后标志物和治疗靶标。这些发现为人类癌症中的翻译后修饰（PTM）提供了有价值的见解，突出新颖的药理学和治疗机会。
■采用基因集变异分析（GSVA）和蛋白质-蛋白质相互作用（PPI）网络分析来鉴定差异表达基因（DEGs）。进行分子对接研究以评估39种化合物与NOTCH3蛋白的结合亲和力。体外试验,包括机动生存能力，基因表达，和细胞凋亡试验，进行评估甘油磷酸肌醇对FGA和NOTCH3表达的影响。此外,拷贝数变异(CNV)，甲基化状态，并对多种癌症类型进行了生存分析。
■在运动诱导的肌肉样本中，NOTCH信号通路持续上调。高NOTCH3表达与COAD患者预后不良相关,细胞外基质组织，免疫浸润，和PI3K-Akt途径的激活。分子对接鉴定了γ-Glu-Trp，γ-谷氨酰酪氨酸,和17-脱氧皮质醇作为NOTCH3的强粘合剂。甘油磷酸肌醇处理调节FGA和NOTCH3表达，影响细胞增殖和凋亡。CNV和甲基化分析揭示了20种癌症类型中FGA和NOTCH3的特定变化。生存分析显示FGA/NOTCH3表达与生存指标之间有很强的关联，FGA负相关，NOTCH3正相关。
■FGA和NOTCH3在运动诱导的肌肉适应和结肠癌进展中起重要作用。这些蛋白质的表达谱和相互作用提供了有希望的预后标志物和治疗靶标。这些发现为人类癌症中的翻译后修饰（PTM）提供了有价值的见解，突出新颖的药理学和治疗机会。
