Hao Lihong, Zhou Xin, Liu Shuqing, Sun Mingzhong, Song Yang, Du Sha, Sun Bing, Guo Chunmei, Gong Linlin, Hu Jun, Guan Hongwei, Shao Shujuan
Key Laboratory for Proteomics of Liaoning Province, Dalian Medical University, Dalian, Liaoning, P. R. China.
Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning, P. R. China.
Proteomics. 2015 Sep;15(17):3087-100. doi: 10.1002/pmic.201400577. Epub 2015 Jun 25.
Glyceraldehyde-3-phosphate dehydrogenase, is one of the most investigated housekeeping genes and widely used as an internal control in analysis of gene expression levels. The present study was designed to assess whether GAPDH is associated with cancer cell growth and progression and, therefore may not be a good internal control in cancer research. Our results from clinical tissue studies showed that the levels of GAPDH protein were significantly up-regulated in lung squamous cell carcinoma tissues, compared with the adjacent normal lung tissues, and this was confirmed by western blotting and immunohistochemistry. GAPDH knockdown by siRNA resulted in significant reductions in proliferation, migration, and invasion of lung squamous carcinoma cells in vitro. In a nude mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell proliferation and migration/invasion in vivo. In summary, GAPDH may not be an appropriate internal control for gene expression studies, especially in cancer research. The role of GAPDH in cancer development and progression should be further examined in pre-clinical and clinical studies.
甘油醛-3-磷酸脱氢酶是研究最多的管家基因之一,在基因表达水平分析中被广泛用作内参。本研究旨在评估甘油醛-3-磷酸脱氢酶(GAPDH)是否与癌细胞的生长和进展相关,因此在癌症研究中可能不是一个好的内参。我们临床组织研究的结果表明,与相邻的正常肺组织相比,肺鳞状细胞癌组织中GAPDH蛋白水平显著上调,这通过蛋白质免疫印迹法和免疫组织化学得到证实。通过小干扰RNA(siRNA)敲低GAPDH导致体外肺鳞状癌细胞的增殖、迁移和侵袭显著减少。在裸鼠癌症异种移植模型中,敲低GAPDH显著抑制体内细胞增殖和迁移/侵袭。总之,GAPDH可能不是基因表达研究的合适内参,尤其是在癌症研究中。GAPDH在癌症发生和进展中的作用应在临床前和临床研究中进一步研究。