GPT2 enhances colorectal cancer cell growth, movement, and invasion by altering gene expression patterns

Glutamic-Pyruvic Transaminase 2 (GPT2) significantly contributes to the advancement of colorectal cancer (CRC). This study aimed to elucidate the expression patterns, functional significance, and underlying mechanisms of GPT2 in CRC. Data from the TCGA repository, supplemented by immunohistochemical analysis, showed that GPT2 is substantially overexpressed in CRC specimens relative to adjacent non-cancerous tissues. This elevated expression level was further correlated with poorer clinical prognosis in patients. Cellular investigations using qPCR and Western blotting revealed differential GPT2 expression across CRC cell lines, with notably high levels in SW620 cells and minimal expression in SW1417 cells. Functional assays revealed that GPT2 overexpression in SW1417 cells notably increased their proliferation, migration, and invasion, while extending the G0/G1 cell cycle phase. Conversely, knocking down GPT2 in SW620 cells suppressed these malignant phenotypes and induced G2/M phase arrest. To investigate the molecular basis, RNA sequencing was performed on GPT2-knockdown SW620 cells, identifying 1020 differentially expressed genes. Enrichment analyses based on GO and the KEGG indicated that the identified genes are predominantly associated with biological processes related to the regulation of blood coagulation and functions localized within the endoplasmic reticulum lumen. Analysis of the PPI network for differentially expressed genes identified five core candidate genes: SERPINE1, CDKN1A, GADD45A, EPHA2, and ASNS. qPCR confirmed the expression levels of these genes, demonstrating a positive correlation with GPT2 expression. In conclusion, GPT2 acts as an oncogenic driver in colorectal cancer, enhancing tumor cell proliferation, migration, and invasive capabilities. This effect is likely mediated through the regulation of downstream targets, including SERPINE1 and CDKN1A. These findings suggest that GPT2 holds potential as both a prognostic indicator and a therapeutic target in colorectal cancer.