SALL4 upregulates brain-derived neurotrophic factor to mediate Hedgehog signaling to inhibit carboplatin sensitivity in colon adenocarcinoma.

Aim: This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) in colon adenocarcinoma, specifically its impact on sensitivity to carboplatin.Methods: mRNA and clinical information of colon adenocarcinoma samples were obtained from TCGA database. Differential expression analysis, transcription factor prediction, gene set enrichment analysis were performed in silico. qRT-PCR, western blot, CCK-8 and CHIP assay were employed.Results: BDNF demonstrated high expression in colon adenocarcinoma. Silencing of BDNF enhanced carboplatin sensitivity, while exerting opposite effects on epithelial-mesenchymal transition (EMT). BDNF was enriched in Hedgehog (HH) signaling pathway. SALL4 was identified as an upstream regulator of BDNF. Upregulation of BDNF by SALL4 promoted EMT and inhibited carboplatin sensitivity.Conclusion: SALL4 promoted BDNF expression to facilitate the aggressive phenotypes of colon adenocarcinoma.