Expression of TRAP1 in colon cancer tissues and its relationship with clinicopathological features and patient prognosis and the possible molecular mechanisms
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Abstract:
Objective: To investigate the expression of tumor necrosis factor receptor associated protein 1 (TRAP1) in colon cancer tissues and its relationship with clinicopathological features and patient prognosis, as well as the related molecular mechanisms.Methods: The expression of TRAP1 in colon cancer and its relationship with clinicopathological features and patient prognosis were comprehensively analyzed by TCGA and GEO databases. In addition, 10 pairs of colon cancer tissues and corresponding paracancerous tissues surgically resected at the First Hospital of Shanxi Medical University between October 2020 and March 2021 were selected, and the expression of TRAP1 in colon cancer tissues of Chinese was detected by IHC staining for validation. Kaplan-Meier survival analysis was performed by running R package (survivor and survminer); The signal peptide and membrane piercing domain of TRAP1 protein were analyzed by online software, and GO analysis and KEGG analysis were carried out by gene enrichment analysis software.Colon cancer SW480 and SW620 cells were cultured and transfected with si-NC or si-TRAP1, and divided into blank control group,si-NC group and si-TRAP1 group. The TRAP1 expression in colon cancer cells of each group after transfection was detected by qPCR,and the cell cycle and apoptosis of the transfected cells were detected by FCM technique. Results: TRAP1 was highly expressed in colon cancer tissues compared with paracancerous tissues (P<0.01). The expression level of TRAP1 was correlated with lymph node etastasis (P<0.05), and the 5-year overall survival (OS) rate of colon cancer patients with high TRAP1 expression was lower than those with low TRAP1 expression (P<0.05). TRAP1 protein is a cytoplasmic protein, and functional enrichment results showed that TRAP1 and its related molecules are associated with signaling pathways such as cell cycle and ribosome biogenesis (all P<0.01). GSEA enrichment results showed that the levels of colon cancer metabolic reprogramming gene cluster and mitochondrial protein input gene cluster were elevated in the high TRAP1 expression group (all P<0.01). Knockdown of TRAP1 resulted in cell cycle arrest in G1 phase with significantly elevated level of apoptosis of colon cancer cells (all P<0.01). Conclusions: TRAP1 is highly expressed in colon cancer tissues and correlated with lymph node metastasis and dismal OS rate in patients. Knockdown of TRAP1 can block cell cycle and promote apoptosis in colon cancer cells.