SOWAHA as a cancer suppressor gene Influence Metabolic Reprogramming

Background: SOWAHA, also known as ANKRD43, is a member of the ankyrin repeat domain family. Studies have indicated that SOWAHA is associated with the microsatellite instability (MSI) status in colorectal cancer patients and could serve as a prognostic biomarker in pancreatic cancer. However, there are rarely reports about SOWAHA in other types of cancer and the specific mechanism of SOWAHA in cancer is also unclear. Methods: Based on National Center for Biotechnology Information (NCBI), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), Integrative Onco Genomics (IntOGen), and other database, we uncovered the potential tumor genomic features of SOWAHA, including the correlation with prognosis, mutation, immune cell infiltration, and DNA methylation, and evaluated the association with tumor heterogeneity and stemness, chemokines chemokine receptors, and immunomodulators in pan-cancer. Besides, we knocked down SOWAHA in SW620 cells and performed RNA-seq analysis, then we conducted functional enrichment to uncover the biological significance of SOWAHA. Results: SOWAHA is a suppressor gene in colorectal carcinoma (COAD), and has early diagnostic potential, with low expression levels linked to poor prognosis in Glioblastoma and Lower Grade Glioma (GBMLGG), Pancreatic adenocarcinoma (PAAD), and other cancers. It is associated with immune cell infiltration, DNA methylation, tumor heterogeneity, and stemness in several epithelial cancers. Furthermore, our experiments revealed that SOWAHA is significantly enriched in the metabolic related pathways in cancer, such as 'P53 signaling pathway', 'PI3K-AKT signaling pathway', and 'pathways in cancer', 'Ubiquitin-Mediated Proteolysis', 'RNA Degradation', etc. We also identified two potential transcription factors regulating SOWAHA, TBX4, and FOXP2, which are misregulated in SW620 cells. Conclusion: SOWAHA, identified as a suppressor gene, may also serve as a valuable biomarker for diagnosis, prognosis, and immunotherapy in some carcinomas, particularly colorectal carcinoma. Its role in the progression of colorectal cancer is primarily mediated through metabolic reprogramming mechanisms.