The mechanism of UCA1/miR-122-5p/CPEB1 axis promoting cisplatin resistance in lung adenocarcinoma
Objective To investigate the mechanism of urothelial carcinomagen1(UCA1)/miR-122-5p/CPEB1 axis promoting cisplatin resistance in lung adenocarcinoma(LAD).Methods UCA1-related miRNA molecules were screened by real-time fluorescence reverse transcription quantitative PCR(RT-qPCR),and miR-122-5p and CPEB1-related cell lines were obtained by cell transfection.The binding of UCA1 to miR-122-5p and CPEB1 to miR-122-5p was verified by dual luciferase reporter assays.Cisplatin drug IC50 concentrations were detedted by drug sensitivity assay.The TCGA database was used to analyze the expression of CPEB1 in lung adenocarcinoma,immune cell function and its relationship with clinical data.Results The expression of miR-122-5p was significantly elevated in LAD cells and the binding of UCA1 to miR-122-5p was verified by dual luciferase reporter assay.MiR-122-5p inhibitor or mimics were transfected to LAD cells;and cisplatin IC50 decreased after miR-122-5p inhibition,whereas cisplatin IC50 increased after miR-122-5p overexpression.The expression level of CPEB1 in LAD cells was significantly decreased.Dual luciferase assay confirmed that CPEB1 bound to miR-122-5p.After overexpression of CPEB1,cisplatin IC50 was decreased.TCGA database showed that the expression of CPEB1 mRNA in LAD tissues was significantly lower than that in adjacent tissues;the expression level of CPEB1 was closely related to the cellular functions such as T,B lymphocytes,CD8+T lymphocytes,natural killer cells,macrophages,neutrophil cells,dendritil cells and mast cells in patients with LAD.ROC curve showed that the expression level of CPEB1 could be used for the diagnosis of LAD(AUC=0.849).Conclusion UCA1 binds to miR-122-5p and target gen CPEB1,which can affect cisplatin resistance in LAD;indicating that UCA1/miR-122-5p/CPEB1 axis may be a potential target for reversing drug resistance.
Urothelial carcinoembryonic antigen 1MiR-122-5pCytosolic polyadenyl element binding protein 1Lung adenocarcinomaCisplatin resistanceMechanism
万方数据
维普
