敲低序列相似家族172成员A抑制肝癌细胞增殖和糖酵解

FAM172A Knockdown Suppresses the Proliferation and Glycolysis of Hepatocellular Carcinoma Cells

序列相似家族172成员A(family with sequence similarity 172 member A,FAM172A)已被证实与多种肿瘤的发生和恶性转化有关,但是FAM172A在肝细胞癌(hepatocellular carcinoma,HCC)中的作用尚不完全清楚。本研究分析了肿瘤与癌症基因组图谱数据库中50例正常肝组织和50例肝癌组织信息,结合实时荧光定量PCR和蛋白质免疫印迹结果,发现肝癌组织中FAM172A的表达高于正常肝组织。利用短发夹RNA(short hairpin RNA,shRNA)将肝癌细胞系中FAM172A进行敲低,细胞活力检测和细胞克隆形成实验结果表明,FAM172A的敲低显著抑制了细胞的增殖(P<0.01)。此外糖酵解压力测试和Western印迹结果显示,敲低FAM172A可以有效抑制肝癌细胞的糖酵解能力,糖酵解酶己糖激酶2(hexokinase 2,HK2)、肝内磷酸果糖激酶(phosphofructokinaseliver,PFKL)、乳酸脱氢酶A(lactate dehydrogenase A,LDHA)及其转录因子c-Myc的表达也明显下调(P<0.001)。过表达c-Myc能够解除敲低FAM172A导致的细胞增殖抑制。综上所述,本文揭示了敲低FAM172A抑制肝癌细胞增殖以及发现FAM172A在肝癌中调控有氧糖酵解的新功能。

Family with sequence similarity 172 member A(FAM172A)has been identified to be associated with tumorigenesis and malignant transformation of multiple tumors,but its role in hepatocellular carcinoma(HCC)remains to be fully elucidated.In this study,the information of 50 normal liver tissues and 50 liver cancer tissues in The Cancer Genome Atlas database was analyzed.Combined with the results of real-time quantitative PCR and Western blot,it was found that the expression of FAM172A in liver cancer tissues was higher than that in normal liver tissues.Short hairpin RNA(shRNA)was used to knock down FAM172A in HCC cell lines.The results of cell viability detection and colony formation assays showed that FAM172A knockdown significantly suppressed cell proliferation(P<0.01).In addition,glycolysis stress test and Western blot results showed that knockdown of FAM172A could effectively inhibit the glycolysis ability of HCC,the expression levels of glycolysis enzyme hexokinase 2,phosphofructokinase-liver,lactate dehydrogenase A and their related transcription factor c-Myc were also significantly down-regulated(P<0.001).Overexpression of c-Myc could relieve the inhibition of cell proliferation caused by FAM172A knockdown.In conclusion,this study revealed the inhibitory effect of FAM172A knockdown on the proliferation of HCC cells and found a new function of FAM172A in regulating aerobic glycolysis in liver cancer.