Hsa_circ_0007401 regulates gemcitabine resistance of pancreatic cancer through the hsa-miR-6509-3p/fli1 axis

Pancreatic cancer is a highly malignant cancer with a poor prognosis. Owing to the strong drug resistance of pancreatic cancer, adjuvant chemotherapy has failed to achieve good results in clinical practice. The expression profile data of circular RNA (circRNA) (GSE110580), microRNA (miRNA) (GSE79234), and messenger RNA (mRNA) (GSE140077, GES35141) were obtained from the gene expression omnibus database. The Cancer-Specific circRNA Database identified the structural pattern of circRNA, and the starBase and circBank databases together predicted the miRNA of circRNA. The mirDIP database predicts the target mRNAs of miRNAs and identifies the ceRNA network of circRNA-miRNA-mRNA via negative regulatory mechanisms. The final validation was performed using clinical data from the cancer treatment response gene signature database of patients treated with gemcitabine for pancreatic cancer of the cancer genome atlas. By differential expression analysis, 22 differential circRNAs (8 upregulated and 14 downregulated), 70 differential microRNAs (37 upregulated and 33 downregulated), and 256 differential messenger RNA (DEmRNA) (161 upregulated and 95 downregulated) were obtained. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses showed that DEmRNAs were associated with drug response, exogenous cellular stimulation, and the tumor necrosis factor signaling pathway. The screened downregulated differential circular RNA (hsa_circ_0007401), upregulated differential microRNA (hsa-miR-6509-3p), and downregulated DEmRNA (FLI1) were consistent with the negative regulation mechanism of the ceRNA network, and FLI1 was significantly downregulated in the data of gemcitabine-resistant pancreatic cancer patients in the cancer genome atlas (n = 26).