IntroductionChemoresistance is a major barrier in the treatment of colorectal cancer (CRC) and many other cancers. ENO1 has been associated with various biological characteristics of CRC. This study aimed to investigate the function of ENO1 in regulating 5-Fluorouracil (5-FU) resistance in CRC.MethodsENO1 level in 120 pairs of tumor tissues and adjacent normal tissues was examined by immunohistochemistry, and the correlation between ENO1 expression and prognosis was explored by survival analysis. Its role and potential mechanisms in regulating 5-FU resistance in CRC were studied by Western blotting, MTT assay, colony formation assay and transwell invasion assay. Murine xenograft assay was implied to verify the results in vivo.ResultsOur study indicated that ENO1 was elevated in CRC tissues and was associated with poor patient prognosis. High levels of ENO1 expression were detected as a significant influencing factor for overall survival. Furthermore, ENO1 expression was found to have increased in drug-resistant cells (HCT116/5-FU and SW620/5-FU) constructed by increasing concentrations of 5-FU. Knockdown of ENO1 markedly increased the drug susceptibility and inhibited the proliferation and migration ability of HCT116/5-FU and SW620/5-FU cells. It was found that down-regulation of ENO1 inhibited the epithelial-mesenchymal transformation (EMT) signaling process. Finally, a murine xenograft assay verified that the depletion of ENO1 alleviated 5-FU resistance.ConclusionThis study identified that ENO1 regulated 5-FU resistance via the EMT pathway and may be a novel target in the prevention and treatment of 5-FUresistant CRC.
Background Gastric cancer (GC) ranks fourth among the causes of death from malignant tumors in the world. Studies have implicated the dysregulation of circRNAs with GC. However, the relationship between hsa‐circ‐0052001 and GC is unclear. Methods In our current study, we assessed the expression levels of hsa‐circ‐0052001 in GC cells and tissues using quantitative real‐time PCR (qPCR). The role of hsa‐circ‐0052001 expression on the proliferation and invasion of GC cells was assessed using in vitro experiments. The role of hsa‐circ‐0052001 on the proliferation of GC cells was also analyzed using in vivo models. The pathways downstream of hsa‐circ‐0052001 were identified using bioinformatics analyses, western blot (WB) assays, and qRT‐PCR. Results We found that compared with normal gastric mucosa epithelial cells and adjacent paracancer tissues, hsa‐circ‐0052001 was overexpressed in GC cells and tissues. Also, the hsa‐circ‐0052001 level was linked to patient clinicopathological characteristics of GC. Cell proliferation and metastatic ability were inhibited in gastric cancer cells when hsa‐circ‐0052001 was knocked down in vitro and cancer growth in vivo. Mechanistically, hsa‐circ‐0052001 promoted the carcinogenesis of GC cells via the MAPK signal pathway. Conclusion Hsa‐circ‐0052001 functions as a tumor gene in promoting the progression of GC through MAPK pathway, which has provided a promising target for patients with GC.
Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although considerable advances in CRC treatment have been achieved, effective treatment improvement has hit a bottleneck. This study demonstrated that TYRO3 expression was aberrantly increased in CRC tissues with prognosis association. The prediction model of prognosis for CRC patients was constructed based on TYRO3 expression. The model suggested that the TYRO3 level is crucial to the final prediction results. We observed that knockdown TYRO3 expression could inhibit the proliferation and migration ability and reverse the drug resistance by constructing drug-resistant CRC cell lines. In vivo experiments also confirmed this conclusion. Thus, targeting TYRO3 combined with 5-Fu treatment could provide a better therapeutic effect. Additionally, TYRO3 could inhibit the EMT process by down-regulating ENO1, which may be achieved by interfering with energy metabolism in cancer cells. Therefore, the current study provides a theoretical basis for TYRO3 in drug-resistance of CRC cells and highlights a new strategy for CRC-targeted therapy.
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