WTAP通过上调糖酵解抑制结直肠癌细胞分化

WTAP inhibits colorectal cancer cell differentiation by up-regulating glycolysis

目的阐明Wilms肿瘤抑制因子1相关蛋白(WTAP)在结直肠癌细胞分化过程中的生物学功能,探索WTAP影响结直肠癌细胞分化的分子机制。方法利用细胞分化模型,检测WTAP在结直肠癌细胞分化过程中的表达模式;构建WTAP过表达、敲降稳转细胞株,通过qRT-PCR和Western blotting方法检测细胞分化指标,分析WTAP对结直肠癌细胞分化状态的影响;通过转录组学方法探索WTAP影响结直肠癌细胞分化的分子机制。结果细胞分化模型显示WTAP的表达水平随着结直肠癌细胞分化显著下调;WTAP过表达可抑制结直肠癌细胞分化,而敲降WTAP则可加速结直肠癌细胞分化进程;转录组学结果提示结直肠癌细胞分化进程中糖酵解途径显著异常,进一步分子生物学验证发现,WTAP可促进结直肠癌细胞糖酵解相关酶的表达。结论WTAP通过促进结直肠癌细胞糖酵解从而抑制细胞分化进程。

Objective To elucidate the biological function of Wilms tumor 1-associating protein(WTAP)in colorectal cancer cell differentiation,and to explore the molecular mechanism of WTAP affecting colorectal cancer cell differentiation.Methods The expression patterns of WTAP in colorectal cancer cell differentiation were detected by cell differentiation model.Stably transfected cell lines with overexpression or knockdown of WTAP were constructed,and the cell differentiation indexes were detected by qRT-PCR and Western blotting to analyze the effects of WTAP on the differentiation status of colorectal cancer cells.Transcriptomics was used to explore the molecular mechanism of WTAP on colorectal cancer cell differentiation.Results The cell differentiation model showed that the expression level of WTAP was significantly down-regulated with colorectal cancer cell differentiation.Overexpression of WTAP could inhibit colorectal cancer cell differentiation,while knockdown of WTAP could accelerate colorectal cancer cell differentiation.The transcriptomics suggested that the glycolytic pathway was significantly abnormal in colorectal cancer cell differentiation.Further molecular biological experiments verified that WTAP could promote the expression of glycolysis-related enzymes in colorectal cancer cells.Conclusion WTAP inhibits cell differentiation by promoting glycolysis in colorectal cancer cells.