JQ1 inhibits the proliferation of thyroid cancer TPC-1 cells by regulating the ferroptosis genes ALOX5 and GDF15

Abstract

Background Thyroid cancer (THCA) is one of the most common malignant endocrine tumors in the world. Current studies suggest that ferroptosis is closely related to the growth and proliferation of cancer cells. The purpose of this study was to find biomarkers that could diagnose the occurrence of THCA and to identify potential compounds that could be used to treat THCA.Methods The GEO, GEPIA, STRING, FerrDb, CPTAC and TIMER databases were used to analyse ferroptosis-related differentially expressed genes (DEGs) in THCA patients. Experiments were used to verify the expression levels of DEGs in THCA tissues and the expression and proliferation ability in cells. The CTD database was used to screen for compounds that modulate DEGs.Results We searched for three DEGs associated with ferroptosis were differentially expressed between THCA and normal tissues. We used TCGA-THCA and GEPIA-THCA datasets to evaluate the findings that ALOX5 and GDF15 gene expression were suitable for further study. We developed a diagnostic prediction model based on ferroptosis-related DEGs with an area under the curve greater than 0.8 and functional enrichment analysis showing correlations with immunity cells. Knockdown of ALOX5 and GDF15 attenuated the proliferative capacity of THCA cells. We used the CTD dataset to identify four compounds that regulate ALOX5 and GDF15, among which JQ1 could be a potential drug for regulating ALOX5 and GDF15 for THCA treatment.Conclusion We constructed a diagnostic model based on ferroptosis-related genes, thereby providing unique insights into the search for potential molecular markers for THCA diagnosis and treatment.