Abstract
Dysregulated glycolysis is one of the mechanisms employed by cancer cells to facilitate growth and metastasis. Here we aimed to characterize the PPFIA4 gene, as a glycolysis-related oncogene in promoting the proliferation and migration of colon cancer cells. Using bioinformatical tools including The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA), we found that PPFIA4 expression and methylation levels were higher in colon cancer tissues of different stages than in normal tissues. Higher PPFIA4 level was also positively correlated with poorer survival of patients. PPFIA4 upregulation also correlated with poor prognosis and higher clinical stages of colon cancer patients. Colon cancer cell viability, migration and migration were enhanced after PPFIA4 overexpression. EMT markers and glycolysis were upregulated after PPFIA4 overexpression. PPFIA4 expression was found to be positively correlated with PFKFB3 and ENO2 levels, while knockdown of PFKFB3 and ENO2 reduced cell proliferation, migration, invasion and glycolysis. PPFIA4 upregulation is a potential biomarker in colon cancer which promotes proliferation, migration, invasion and glycolysis. The upregulation of PFKFB3/ENO2 signaling by PPFIA4 is a potential mechanism underlying the oncogenic effects of PPFIA4.
Highlights
Colon cancer is the fourth leading cause of cancer-related deaths worldwide, and new biomarkers for colon cancer are still urgently needed to development effective means to improve treatment outcomes
We validated that PPFIA4 was highly correlated with the survival and prognosis of colon cancer patients, and this study focused on evaluating the role of PPFIA4 in promoting proliferation, migration and invasion of colon cancer cells
We first used the Gene Expression Profiling Interactive Analysis (GEPIA) dataset to screen for the top 100 most differential survival genes (MDSGs) in colon cancer, which significantly correlated with overall survival (OS) and diseasefree survival (DFS) of patients (Figure 1A)
Summary
Colon cancer is the fourth leading cause of cancer-related deaths worldwide, and new biomarkers for colon cancer are still urgently needed to development effective means to improve treatment outcomes. The Cancer Genome Atlas (TCGA) [1] and Gene Expression Profiling Interactive Analysis (GEPIA) [2] have tremendously facilitated the discovery of new genes aberrantly expressed in colon cancer, which have potential to become novel diagnostic and therapeutic targets, providing molecular basis for targeted therapies and advanced precision medicine for colon cancer treatment. Among oncogenes identified in colon cancer, genes that regulate cancer cell metabolism have garnered growing interest as it is increasingly recognized that dysregulated cellular energetics metabolism is fundamentally connected to cancer proliferation, epigenetics and survival of patients [3]. Lactate, the product of glycolysis, stimulates tumor invasion by enhancing migratory ability, immune escape, angiogenesis and radioresistance [6]
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