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Transcription Factors and MiRNAs Regulate the Mechanism of Drug Resistance in Oesophageal Cancer

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Yanwei Zhao, Zhenxing Wang, Xizi Wang, Xiaodong Jia, Mingjun Li


The presence of drug resistance can lead to differences in treatment outcomes among patients using the same drug. Therefore, identification of key biological markers associated with drug resistance can help clinicians to quickly select the appropriate drug to prolong the survival time of patients, and it is important for drug development and detailed study of the drug’s mechanism of action. Firstly, we screened different drug resistance and sensitive cell lines in esophageal cancer cell lines to find different drug resistance related genes, and annotated these calculated drug resistance related genes into the transcriptional regulatory network we constructed. The regulatory relationships within this transcriptional regulatory network were all experimentally confirmed and further filtered by real esophageal cancer data to identify drug resistance related modules and key regulators. Thirteen drug resistance-associated modules were identified, each containing 1-6 drug resistance-associated key regulators. Among them, transcription factors SP1, has-miR-21-5p and hsa-miR-1-5p play key regulatory roles in the resistance modules of various drugs, and they regulate drug resistance-associated differentially expressed genes through one-step or multi-step regulatory relationships. Key transcription factors and miRNA in the transcriptional regulatory network that regulate drug resistance-associated genes can be used as potential biomarkers to identify drug resistance to the corresponding drugs in tumor patients.


Drug resistance, miRNA, Transcription factor, Regulatory network

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