摘要目的:探讨组蛋白赖氨酸去甲基化酶4A(KDM4A)在结直肠癌发生发展中的作用及可能的机制。方法:2019年1月至2019年6月，构建高(KDM4A)、低表达(ShKDM4A#1，ShKDM4A#2)KDM4A的结直肠癌细胞株(购自美国典型菌种保藏中心公司)，同时设立对照组(NC，ShNC)。通过四甲基偶氮唑盐微量酶反应比色法(MTT)检测KDM4A对细胞增殖的影响。利用细胞侵袭小室法(Transwell)检测KDM4A对结直肠癌细胞迁移/侵袭能力的影响。通过蛋白质印迹法(Western blot)检测高、低表达KDM4A后细胞周期蛋白D1(Cyclin D1)和基质金属蛋白酶-9(MMP-9)的表达。两组间统计学差异通过双尾 t检验进行分析。 结果:KDM4A高表达组与对照组比较，细胞增殖率明显提高[(50.233±3.430)%和(35.417±4.501)%， t＝3.900、2.942， P<0.05]。低表达KDM4A与对照组比较，细胞增殖能力明显受抑制[(58.056±2.750)%和(57.386±8.228)%， t＝4.558、4.419， P<0.05]。Transwell实验显示高表达KDM4A后穿孔细胞数[(304.000±62.466)个]比对照组[(64.000±20.833)个]增多( t＝5.154， P<0.01)；低表达KDM4A后穿孔细胞数[(47.333±13.573)个]较对照组[(93.667±18.874)个]减少( t＝2.819， P<0.05)。KDM4A可以正向调节Cyclin D1和MMP-9的蛋白表达。 结论:KDM4A在结直肠肿瘤发生发展中起到重要作用，其机制可能是通过调节Cyclin D1和MMP-9的表达。

abstractsObjective:To determine the role and possible mechanism of Lysine demethylase 4A (KDM4A) in the progression of colorectal cancer.Methods:Colorectal cancer cell lines with high (KDM4A) and low expression (ShKDM4A#1, ShKDM4A#2) of KDM4A were constructed from January 2019 to June 2019, and the control groups (NC, ShNC) were also established. The effect of KDM4A on cell proliferation was determined by the 3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Transwell experiments were performed to detect the effect of KDM4A on migration and invasion of colorectal cancer cells. The expression levels of Cyclin D1 and Matrix metalloproteinase-9 (MMP-9) were detected by Western blotting after high and low expression of KDM4A. SPSS 24.0 software was used for statistical analysis, and the statistical differences between the two groups were analyzed by t test. Results:As compared with the control group, the proliferation of highly expressed KDM4A cells was enhanced [(50.233±3.430)% and (35.417±4.501)%, t=3.900, P<0.05 and t=2.942, P<0.05]. On the contrary, the proliferation of cells with KDM4A knock-down was inhibited [(58.056±2.750)% and (57.386±8.228)%, t=4.558, P<0.05 and t=4.419, P<0.05]. Furthermore, Transwell assay revealed that the number of migrating SW480 cells in KDM4A overexpression group (304.000±62.466) was significantly greater than that in control group (64.000±20.833, t=5.154, P<0.01). The number of invasive SW48 cells in KDM4A knock-down group (47.333±13.573) was less than that in control group (93.667±18.874, t=2.819, P<0.05). KDM4A positively regulated the protein expression of Cyclin D1 and MMP-9. Conclusion:KDM4A plays an important role in the development of colorectal tumors, possibly by regulating the expression of Cyclin D1 and MMP-9.