miR-124调控GATA6在胆管癌侵袭转移中的作用及机制研究

The treatment of cholangiocarcinoma(CCA)is often ineffective because of the early and strong invasiveness of the tumor. Our previous study showed that GATA6 was overexpressed in CCAs and promoted CCA invasion and metastasis. Genomic DNA copy number amplifications of GATA6 in CCAs has been reported that led to GATA6 overexpression, but negative regulation of GATA6 is still unclear. MicroRNAs (miRNAs) regulate gene expression negatively. Our pre-experiment found the expression of miR - 124 was lower in CCAs cells than biliary epithelial cells and upregulation of miR - 124 in CCAs cells could make the invasion decline , the expression of GATA6 down at the same time. In present study ,we postulates that miR-124 influences invasion and metastasis of CCA through regulating GATA6.We will demostrate the relationship between miR-124 and GATA6 in clinical CCA specimens and CCA cell line with different metastatic potentials using luciferase reporter gene assay ,point mutation and other methods.The aim of this study is to enrich the pathogenesis of CCA metastasis and also to provide more potential research evidence for clinical therapy of CCA.

胆管癌因侵袭转移导致治疗效果差。我们前期研究发现胆管癌中GATA6异常表达，促进侵袭转移，与病人预后不良显著相关；文献报道胆管癌中GATA6基因拷贝数明显增加，导致GATA6表达明显上调，而GATA6的负性调控机制尚不清楚。MicroRNA是病理生理过程中蛋白表达的一种重要的负性调控因素。我们前期预实验发现人胆管癌细胞中miR-124表达显著降低，上调miR-124后，细胞侵袭能力下降，同时GATA6表达水平降低。本项目提出"miR-124通过调控GATA6影响胆管癌的侵袭转移"假说，拟以胆管癌组织及不同转移潜能的细胞株为研究对象，采用定点突变、荧光素酶报告基因检测实验等分子生物学手段，确立miR-124与GATA6的调控关系，最终探明miR-124通过调控GATA6基因的表达影响了胆管癌的转移，有望深入认识胆管癌的侵袭转移机制，并为胆管癌侵袭转移提供新的治疗靶点。

胆管癌因侵袭转移导致治疗效果差。我们前期研究发现胆管癌中GATA6 异常表达，促进其侵袭转移，与病人预后不良显著相关。然而胆管癌中GATA6的调控机制尚不清楚。为此本研究探讨了胆管癌中miR-124对其侵袭转移的作用及GATA6的调控机制。发现胆管癌中miR-124表达显著降低，miR-124能直接调控GATA6的表达来抑制胆管癌的侵袭转移。本研究深入认识了胆管癌的侵袭转移机制，并为胆管癌侵袭转移提供一种新的可能的治疗靶点。