Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a major health issue that has been eluding efforts to identify viable therapeutic treatment options. Besides having the lowest survival rate among all types of cancer, almost all conventional methods of treatment are futile against this condition, leaving patients to succumb to this ailment faster than ever. As it is increasingly becoming difficult to come up with new compounds for the treatment of various diseases, alternative solutions are required for tackling these problems. In this study, publically available miRNA and gene expression data were used to identify common elements that were present in gemcitabine-resistant PDAC cell lines. By selecting overexpressed genes involved in pancreatic cancer and cancer pathways in general, potential drug candidates for the treatment of PDAC were identified. In this study, 21 differentially expressed miRNAs were identified from PANC-1 cell line treated with gemcitabine. Pathway analysis revealed that MET and PPARG were overexpressed in cancer-related pathways, including pancreatic cancer, and could be targeted for PDAC treatment. Using CMap, fisetin was identified a likely candidate drug for the treatment of PDAC. Docking studies indicated that fisetin was bound to c-Met and PPARG with an XP G score of –12.819 and –7.021 kcal/mol, respectively. As miRNAs have increasingly been shown to part take in important cancer-related processes and pathways, researching drug development methods based on miRNA targets could be beneficial for pharmaceutical industries.

Communicated by Ramaswamy H. Sarma

摘要

胰腺导管腺癌 (PDAC) 是一个主要的健康问题，一直在努力确定可行的治疗方案。除了在所有类型的癌症中存活率最低之外，几乎所有传统的治疗方法都对这种情况无效，使患者比以往任何时候都更快地死于这种疾病。随着开发用于治疗各种疾病的新化合物变得越来越困难，需要替代解决方案来解决这些问题。在这项研究中，公开可用的 miRNA 和基因表达数据用于鉴定存在于耐吉西他滨的 PDAC 细胞系中的常见元件。通过选择涉及胰腺癌和一般癌症途径的过表达基因，确定了治疗 PDAC 的潜在候选药物。在这项研究中，从用吉西他滨处理的 PANC-1 细胞系中鉴定了 21 种差异表达的 miRNA。通路分析表明MET和PPARG在包括胰腺癌在内的癌症相关通路中过度表达，可以作为 PDAC 治疗的目标。使用 CMap，fisetin 被确定为治疗 PDAC 的可能候选药物。对接研究表明非瑟酮与 c-Met 和 PPARG 结合，XP G 评分分别为 –12.819 和 –7.021 kcal/mol。随着 miRNA 越来越多地被证明参与重要的癌症相关过程和途径，研究基于 miRNA 靶点的药物开发方法可能对制药行业有益。

由 Ramaswamy H. Sarma 交流