Integration of transcriptomics and metabolomics reveals anlotinib-induced cytotoxicity in colon cancer cells.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Zhenxian Jia, Zhi Zhang, Qinqin Tian, Hongjiao Wu, Yuning Xie, Ang Li, Hongmei Zhang, Zhenbang Yang, Xuemei Zhang
• Journal: Gene (Gene) Vol. 786 Pg. 145625 (Jun 20 2021) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 33798683 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Cell Cycle Proteins
• Chondroitin Sulfate Proteoglycans
• Chromosomal Proteins, Non-Histone
• Indoles
• Poly-ADP-Ribose Binding Proteins
• Quinolines
• SMC3 protein, human
• anlotinib
• Glutamine
• Aspartic Acid
• Glycogen Phosphorylase
• DNA Topoisomerases, Type II
• TOP2A protein, human

Topics

• Aspartic Acid (metabolism)
• Cell Cycle Proteins (genetics)
• Chondroitin Sulfate Proteoglycans (genetics)
• Chromatography, Liquid
• Chromosomal Proteins, Non-Histone (genetics)
• Colonic Neoplasms (chemistry, drug therapy, genetics)
• DNA Topoisomerases, Type II (genetics)
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Regulatory Networks
• Glutamine (metabolism)
• Glycogen Phosphorylase (genetics)
• HCT116 Cells
• Humans
• Indoles (pharmacology)
• Metabolomics (methods)
• Poly-ADP-Ribose Binding Proteins (genetics)
• Quinolines (pharmacology)
• Sequence Analysis, RNA
• Tandem Mass Spectrometry