Methylation Drives SLC2A1 Transcription and Ferroptosis Process Decreasing Autophagy Pressure in Colon Cancer.
Junwei ZouZhenhan LiJiaheng XieZhaoying WuYujin HuangHao XieHuiqiu XuYong HuangHailang ZhouPublished in: Journal of oncology (2022)
Colon cancer is a common malignant tumor in the digestive tract, with relatively high rates of morbidity and mortality. It is the third most common type of tumor in the world. The effective treatment of advanced colon cancer is limited, so it is particularly important to study the new pathogenesis of colon cancer. Ferroptosis is a nonapoptotic regulated cell death mode driven by iron-dependent lipid peroxidation, a process which has been discovered in recent years. Autophagy involves lysosomal degradation pathways that promote or prevent cell death. High levels of autophagy are associated with ferroptosis, but a clear association has not yet been made between ferroptosis and autophagy in colon cancer. Through the analysis of transcriptome expression profiling data in colon cancer, we obtained the common upregulated genes and downregulated genes by recording the intersection of the differentially expressed genes in each dataset. Solute Carrier Family 2 Member 1 (SLC2A1) was identified by combining autophagy genes obtained from GeneCards and ferroptosis genes obtained from FerrDb. In order to explore the clinical significance and prognostic value of SLC2A1, we utilized massive databases to conduct an in-depth exploration of the methylation of SLC2A1, and we also investigated the differences in immune infiltration between tumor and normal tissues. We found that there are abundant methylation sites in SLC2A1 and that the methylation of SLC2A1 is correlated with the immunosuppression of tumor tissue. We discovered that during the induction of environmental factors, the transcription and methylation levels of SLC2A1 were greatly increased, autophagy and ferroptosis were inhibited, and the immune system was defective, resulting in a poor prognosis for patients. These results suggest that the autophagy and ferroptosis-related gene SLC2A1 is involved in the tumor immune regulation of colon cancer, and SLC2A1 may become a new therapeutic target for colon cancer.
Keyphrases
- cell death
- genome wide
- dna methylation
- cell cycle arrest
- genome wide identification
- poor prognosis
- transcription factor
- bioinformatics analysis
- endoplasmic reticulum stress
- prognostic factors
- end stage renal disease
- oxidative stress
- cell proliferation
- machine learning
- ejection fraction
- rna seq
- peritoneal dialysis
- newly diagnosed
- mass spectrometry
- deep learning
- single molecule
- patient reported outcomes
- electronic health record
- artificial intelligence
- replacement therapy