SALL4 upregulates brain-derived neurotrophic factor to mediate Hedgehog signaling to inhibit carboplatin sensitivity in colon adenocarcinoma.
Minhan ChenYing LiuWeihua XingPublished in: Pharmacogenomics (2024)
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.
Keyphrases
- epithelial mesenchymal transition
- stress induced
- squamous cell carcinoma
- signaling pathway
- poor prognosis
- transcription factor
- locally advanced
- phase ii study
- high throughput
- binding protein
- gene expression
- clinical trial
- cell proliferation
- randomized controlled trial
- emergency department
- phase iii
- genome wide identification
- dna methylation
- copy number
- dna binding