SOWAHA as a Cancer Suppressor Gene Influence Metabolic Reprogramming

TL;DR

This study investigates SOWAHA as a tumor suppressor gene influencing metabolic reprogramming in cancer, revealing its diagnostic potential, association with immune infiltration, and underlying mechanisms through bioinformatics and experimental validation.

Contribution

It uncovers the tumor suppressor role of SOWAHA in cancer, especially colorectal, and elucidates its involvement in metabolic pathways and immune interactions using comprehensive bioinformatics and cell experiments.

Findings

Low SOWAHA expression correlates with poor prognosis in several cancers.

SOWAHA is linked to immune cell infiltration and tumor heterogeneity.

Knockdown of SOWAHA affects metabolic pathways and cell proliferation.

Abstract

SOWAHA is a protein-coding gene, also known as ANKRD43. Studies have indicated that SOWAHA can serve as a prognostic biomarker in colorectal cancer and pancreatic cancer. However, there are few reports about SOWAHA in other types of cancer and the specific mechanism of action of SOWAHA in cancer is also not clear. Based on National Center for Biotechnology Information (NCBI), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), etc., we adopted bioinformatics methods to uncover the potential tumor genomic features of SOWAHA, including the correlation with prognosis, gene mutation, immune cell infiltration, and DNA methylation in different tumors and evaluated the association with tumor heterogeneity, 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 the gene set. SOWAHA has early diagnostic potential, and low expression of SOWAHA was associated with poor prognosis in was associated with poor prognosis in GBMLGG, PAAD, READ, etc. SOWAHA is associated with most tumor immune-infiltrating cells in pan-cancer. SOWAHA correlates with DNA methylation, tumor heterogeneity, and stemness in many epithelial carcinomas. Furthermore, SOWAHA is involved in many enzyme activity and metabolic pathways, mainly metabolic programming pathways in cancer. Additionally, we identified two potential transcription factors of SOWAHA, TBX4, and FOXP2, which are dysregulated in SW620 cells. Besides, the cell proliferation and viability in siSOWAHA groups are better than in siNC groups.SOWAHA, identified as a suppressor gene, and its role in the progression of colorectal cancer is primarily mediated through metabolic reprogramming mechanisms.