کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3446306 1595456 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aberrant Expression of CUL4A Is Associated with IL-6/ STAT3 Activation in Colorectal Cancer Progression
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
Aberrant Expression of CUL4A Is Associated with IL-6/ STAT3 Activation in Colorectal Cancer Progression
چکیده انگلیسی

Background and AimsAlthough it has been indicated that the cytokine interleukin-6 (IL-6) promotes colorectal cancer (CRC) tumorigenesis in tumor microenvironment, the mechanisms related to IL-6-induced tumor progression are still not well understood.MethodsFirst, the correlation between pSTAT3, CUL4A and ZEB1 was analyzed using immunocytochemistry. Logistic regression analysis was then used to observe the relationship between levels of pSTAT3, CUL4A and ZEB1 and clinicopathological characteristics. Finally, the mechanism of the effect of the expression level of pSTAT3, CUL4A and ZEB1 on cell invasion ability was verified by cell experiment.ResultsWe discovered that the increased expression levels of pSTAT3, CUL4A and ZEB1 had significant relationships in CRC patients. These up-regulated expression levels were also closely associated with CRC aggressiveness. Furthermore, in vitro, we discovered that expression levels of CUL4A and ZEB1 were significantly up-regulated when IL-6 stimulated. However, the CUL4A–knockdown, IL-6, could not induce expression of ZEB1. CHIP assay authenticated that pSTAT3 could bind to CUL4A promoter and worked as their transcription factors. We also demonstrated that IL-6 markedly increased the reporter activity using a luciferase reporter gene containing CUL4A promoter. Finally, silencing CUL4A blocked IL-6-driven invasion in matrigel invasion assay.ConclusionThis study proposed that CUL4A played an oncogene role through ZEB1 in IL-6-induced colorectal carcinoma progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Medical Research - Volume 47, Issue 3, April 2016, Pages 214–222
نویسندگان
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