miR let-7家族在胰腺导管腺癌发生发展中的作用

The Mechanism of miR let-7 Family in Pancreatic Ductal Adenocarcinoma

目的在大规模表达谱芯片中寻找与胰腺导管腺癌(PDAC)相关的RNA分子,并探讨其分子机制。方法基于RNA的表达谱数据,构建"转录因子-miRNA-mRNA"调控关系网络,挖掘与PDAC相关的mRNA及miRNA。结果 6个miR let-7家族miRNA成员(hsa-let-7i、hsa-let-7d、hsa-let-7b、hsa-let-7g、hsa-let-7c、hsa-let-7e)参与一个核心调控网络,其网络中涉及的基因和其他miRNA均为与PDAC发生发展相关的分子。其中处于网络核心位置的基因ALDH1A1、ZEB1、HMGA2、EGR1和TGFB1,与PDAC的发展及预后直接相关。网络中的hsa-mir-200b、hsa-mir-200a可与ZEB1基因相互调控,通过Notch信号通路影响PDAC的发展及转移。结论 miR let-7家族miRNA分子可能与ALDH1A1、ZEB1与HMGA2等分子相互调控,并与PDAC的发生发展密切相关。

Objective To identify candidate molecules related to pancreatic ductal adenocarcinoma （ PDAC） and investi-gate the molecular mechanism of the candidate molecule by large-scale expression profiles .Methods miRNA and mRNA expres-sion of PDAC was used to construct the molecular regulatory network by the interaction of ‘transcription factor target miRNA ’ and‘mRNA target gene ’ ,and identify some candidate genes and miRNAs related to PDAC .Results There were 6 kinds of miR let-7（hsa-let-7i、hsa-let-7d、hsa-let-7b、hsa-let-7g、hsa-let-7c、hsa-let-7e）,all genes and miRNA were related to PDAC development . ALDH1A1、ZEB1、HMGA2、EGR1 and TGFB1 were directly related to PDAC development and prognosis .has-mir-200b and has-mir-200a interacted with ZEB1,and influenced the prognosis of PDAC through Notch signaling pathway .Conclusion miR let-7 family may interact with ALDH1A1、ZEB1、HMGA2,and are related the PDAC development .