RESUMO
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.
[Box: see text].
Assuntos
Adenocarcinoma , Fator Neurotrófico Derivado do Encéfalo , Carboplatina , Neoplasias do Colo , Proteínas Hedgehog , Transdução de Sinais , Fatores de Transcrição , Regulação para Cima , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Carboplatina/uso terapêutico , Carboplatina/farmacologia , Proteínas Hedgehog/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Fatores de Transcrição/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacosAssuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Blastoma Pulmonar , Compostos Radiofarmacêuticos , Humanos , Blastoma Pulmonar/diagnóstico por imagem , Blastoma Pulmonar/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Adulto , Diagnóstico DiferencialRESUMO
Colorectal carcinoma (CRC) is a fatal disease and ranks as the third most prevalent cancer globally. Stemness and drug resistance are the main causes of tumor recurrence in CRC. This study attempted to probe the impact of TWIST1 on CRC stemness and resistance to oxaliplatin and to uncover the underlying regulatory mechanism of TWIST1. mRNA expression data from The Cancer Genome Atlas-CRC were subjected to differential analysis. The target gene in the study was determined according to literature citation. ChIPBase was utilized to predict likely targets downstream of the target gene. Pearson was employed for correlation analysis. Quantitative real-time polymerase chain reaction was used to assess TWIST1 and microfibrillar-associated protein 2 (MFAP2) levels in CRC and normal cells. The cell viability was assayed through cell counting kit-8 and IC50 value was calculated. Flow cytometry was applied to assay the cell apoptosis. Apoptosis assays were applied to evaluate cell apoptosis. CD44, CD133, SOX-2, ERCC1, GST-π, MRP, and P-gp protein expression levels were assayed by Western blot. The targeting relationship between TWIST1 and MFAP2 was ascertained through dual-luciferase and chromatin immunoprecipitation (ChIP). TWIST1 possessed high expression in CRC tissue and cells. TWIST1 knockdown strikingly promoted cell apoptosis and reduced cell stemness and cell resistance to oxaliplatin. Bioinformatics prediction suggested that MFAP2, which was overexpressed in CRC tissue and cells, was the target gene downstream of TWIST1. Dual-luciferase and ChIP assays validated that there was a targeting relationship between TWIST1 and MFAP2. The results of the rescue assay demonstrated that TWIST1 fostered CRC stemness and oxaliplatin resistance by activating MFAP2 expression. These outcomes implied that TWIST1 enhanced CRC stemness and oxaliplatin resistance by activating the transcription of MFAP2. Therefore, TWIST1/MFAP2 axis possibly indicated a mechanism for regulating tumor progression.