School of Public Health, North China University of Science and Technology, Tangshan 063210, China; College of Life Science, North China University of Science and Technology, Tangshan 063210, China.
Affliated Tangshan Gongren Hospital, North China University of Science and Technology, Tangshan 063000, China.
Gene. 2021 Jun 20;786:145625. doi: 10.1016/j.gene.2021.145625. Epub 2021 Mar 30.
Mounting evidences suggested that anlotinib exhibits effective anti-tumor activity in various cancer types, such as lung cancer, glioblastoma and medullary thyroid cancer. However, its function in colon cancer remains to be further revealed.
Colon cancer cells (HCT-116) were treated with or without anlotinib. Transcript and metabolite data were generated through RNA sequencing and liquid chromatography-tandem mass spectrometry, respectively. The integrated analysis transcriptomics and metabolomics was conducted using R programs and online tools, including ClusterProfiler R program, GSEA, Prognoscan and Cytoscape.
We found that differentially expressed genes (DEGs) were mainly involved in metabolic pathways and ribosome pathway. Structural maintenance of chromosome 3 (SMC3), Topoisomerase II alpha (TOP2A) and Glycogen phosphorylase B (PYGB) are the most significant DEGs which bring poor clinical prognosis in colon cancer. The analysis of metabolomics presented that most of the differentially accumulated metabolites (DAMs) were amino acids, such as L-glutamine, DL-serine and aspartic acid. The joint analysis of DEGs and DAMs showed that they were mainly involved in protein digestion and absorption, ABC transporters, central carbon metabolism, choline metabolism and Gap junction. Anlotinib affected protein synthesis and energy supporting of colon cancer cells by regulating amino acid metabolism.
Anlotinib has a significant effect on colon cancer in both transcriptome and metabolome. Our research will provide possible targets for colon cancer treatment using anlotinib.
越来越多的证据表明，安罗替尼在多种癌症类型中具有有效的抗肿瘤活性，如肺癌、胶质母细胞瘤和髓样甲状腺癌。然而，其在结肠癌中的作用仍有待进一步揭示。
用或不用安罗替尼处理结肠癌细胞（HCT-116）。通过 RNA 测序和液相色谱-串联质谱分别生成转录组和代谢物数据。使用 R 程序和在线工具（包括 ClusterProfiler R 程序、GSEA、Prognoscan 和 Cytoscape）对转录组学和代谢组学进行综合分析。
我们发现差异表达基因（DEGs）主要参与代谢途径和核糖体途径。结构维持染色体 3（SMC3）、拓扑异构酶 II alpha（TOP2A）和糖原磷酸化酶 B（PYGB）是结肠癌中具有最差临床预后的最显著 DEGs。代谢组学分析表明，大多数差异积累代谢物（DAMs）是氨基酸，如 L-谷氨酰胺、DL-丝氨酸和天冬氨酸。DEGs 和 DAMs 的联合分析表明，它们主要参与蛋白质消化和吸收、ABC 转运体、中心碳代谢、胆碱代谢和间隙连接。安罗替尼通过调节氨基酸代谢影响结肠癌细胞的蛋白质合成和能量供应。
安罗替尼在转录组和代谢组水平上对结肠癌均有显著作用。我们的研究将为使用安罗替尼治疗结肠癌提供可能的靶点。
