HMGA2通过激活Wnt信号通路促进结直肠癌细胞增殖

摘要

Objective:HMGA2 (high-mobility group AT-hook 2) is a chromosome protein which has been well-documented to regulate cancer progression.We investigated whether and how HMGA2 affects Wnt signaling transduction process and the proliferation of colorectal cancer cells.Methods:RT-qPCR and western blot were utilized to examine mRNA and protein expression levels changes of HMGA2 in colorectal cancer tissues compared to nearby normal tissues.TOPflash reporter assay was conducted to detect the regulatory function of HMGA2 in Wnt signaling.Cell proliferation was quantified by Cell Counting Kit-8 in SW480 cells infected by adenovirus containing HMGA2 expression construct.Results:We found that both the mRNA and protein of HMGA2 were highly expressed in most of the examined human colorectal cancer samples.HMGA2 increased the expression of TOPflash a dose-dependent manner.And knockdown HMGA2 expression reduced Wnt3a-,LiCl-,βcatenin-or Dvl (Dishevelled)-activated TOPflash-luciferase expression in colorectal cancer cell line HCT-116.Furthermore,ectopic expression of HMGA2 promoted proliferation of colorectal cancer cell line SW480.Conclusions:HMGA2 gene was highly expressed in the majority of the examined colorectal cancer samples.HMGA2 can promote the proliferation of colorectal cancer cells by up-regulating Wnt signaling.These results reveal the molecular and pathological functions of HMGA2 in colorectal cancer development and a potentially new regulatory effect on Wnt signaling.%目的:HMGA2(high-mobility group AT-hook 2)一个染色质蛋白,被报道在多种癌症中都发挥重要作用.本文研究染色体蛋白HMGA2对Wnt信号传递的影响,及对结直肠癌细胞增殖的影响.方法:本文通过qRT-PCR和免疫印迹法检测HMGA2在结直肠癌样本中mRNA和蛋白水平.用荧光素酶报告基因系统研究HMGA2对Wnt信号通路的作用.用细胞增殖实验检测HMGA2 对结直肠癌细胞增殖的作用.结果:在我们检测的大部分结直肠癌样本里,HMGA2表达水平升高;HMGA2蛋白可上调Wnt信号通路荧光素酶报告基因TOPflash-luciferase的表达,并呈现剂量依赖的形式.降低HMGA2表达可抑制由Wnt3a、Dvl (Dishevelled)、LiCl以及βcatenin(S37A)引起的TOPflash-luciferase报告基因表达上调作用.此外,SW480中过量表达HMGA2可以促进细胞增殖.结论:HMGA2在结直肠癌中表达升高,HMGA2在结直肠癌中通过增强Wnt信号来促进结直肠癌细胞的增殖.