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- W4386135523 abstract "Abstract Background Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigates the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. Methods We extracted differentially expressed genes (DEGs) from the GSE140973 and identified the overlapping genes combined with 151 Wnt/β-Catenin signaling pathway-related genes. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene and scrutinized the impact of cetuximab and the hub gene on CRC cellular progression through cell experimental. Results Our study identified 26 overlapping genes. High expression of 8 genes (AXIN1, CACYBP, FBXW11, FZD2, MAPK9, PLCB3, NCOA3, RHOA) correlated with poorer prognosis, whereas high expression of TCF7L2 indicated better prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both β-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings reveal PLCB3 promotes cetuximab inhibition on Wnt/β-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. Conclusion Our study emphasizes the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppresses Wnt/β-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offers fresh perspectives on cetuximab mechanism in CRC." @default.
- W4386135523 created "2023-08-25" @default.
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- W4386135523 date "2023-08-24" @default.
- W4386135523 modified "2023-09-27" @default.
- W4386135523 title "Cetuximab inhibits colorectal cancer development through inactivating the Wnt/β-catenin pathway and modulating PLCB3 expression" @default.
- W4386135523 doi "https://doi.org/10.21203/rs.3.rs-3258212/v1" @default.
- W4386135523 hasPublicationYear "2023" @default.
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