| 引用本文: | 赵燕伟,王振兴,王熙梓,贾晓东,李明君.转录因子及miRNA调控食管癌耐药机制研究[J].生物信息学,2022,20(1):56-63. |
| ZHAO Yanwei,WANG Zhenxing,WANG Xizi,JIA Xiaodong,LI Mingjun.Role and mechanisms of miRNA and transcription factorsregulating drug resistance of esophageal cancer[J].Chinese Journal of Bioinformatics,2022,20(1):56-63. |
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| 摘要: |
| 由于耐药性的存在,不同患者在使用相同药物时会导致治疗效果的差异。因此识别耐药性相关的关键生物学标记,有助于临床医生快速选择出适合的药物,延长患者的生存时间,对药物研发以及药物的作用机制的详细研究具有重要意义。首先在食管癌细胞系中筛选不同药物的耐药及敏感细胞系,从中找到不同药物耐药相关的基因,将这些计算得到的耐药相关基因注释到我们构建的转录调控网络内,这一转录调控网络内的调控关系均为实验证实的,而且经过了真实的食管癌数据进行了进一步过滤,从网络内识别出药物耐药相关的模块及关键的调控子。识别了13种药物的耐药性相关模块,每种药物的模块中包含1-6个耐药相关的关键调控子。其中转录因子SP1、 hsa-miR-21-5p、hsa-miR-1-5p在多种药物的耐药性模块中都起到了关键的调控作用,它们通过一步或者多步的调控关系调控耐药相关的差异表达基因。转录调控网络中调控耐药相关基因的关键转录因子和miRNA,可作为潜在的生物标记物来识别肿瘤患者对相应药物的耐药性。 |
| 关键词: 耐药 miRNA 转录因子 调控网络 |
| DOI：10.12113/202009005 |
| 分类号:Q42 |
| 文献标识码:A |
| 基金项目: |
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| Role and mechanisms of miRNA and transcription factorsregulating drug resistance of esophageal cancer |
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ZHAO Yanwei, WANG Zhenxing, WANG Xizi, JIA Xiaodong, LI Mingjun
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(Liaocheng People’s Hospital, Liaocheng 252000, Shandong, China)
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| Abstract: |
| The existence of drug resistance causes differences in the treatment of patients when using the same drug. Therefore, the identification of key biological markers related to drug resistance can help doctors quickly select suitable drugs and prolong the survival time of patients, which is of great significance for drug research and development as well as the detailed study of drug mechanism. Firstly, the drug-resistant and sensitive esophageal cancer cell lines of different drugs were screened to identify drug resistance associated genes for each drug. Then, these genes were mapped into the transcriptional regulatory network,which was constructed in the study. The regulatory relationship in the network was confirmed by experiments,and further filtered via actual esophageal cancer data. Drug resistance associated modules and key regulators were identified from the network. A total of 13 drug resistance-related modules were identified, which contained 1-6 key regulators for each module. Among them, transcription factor SP1, hsa-miR-21-5p, and hsa-miR-1-5p genes played a key regulatory role in multiple drug resistance modules. Many differentially expressed genes related to drug resistance were regulated by them through one-step or multi-step regulatory relationship. Key transcription factors and miRNAs that regulate drug resistance-related genes in the transcriptional regulatory network can be used as new biomarkers to identify the resistance of tumor patients to the corresponding drugs. |
| Key words: Drug resistance miRNA Transcription factor Regulatory network |
