三甲基转移酶SETD2表达下调促进结肠直肠癌细胞的迁移和增殖

Downregulation of trimethyl transferase SETD2 promotes migration and proliferation of colorectal cancer cell

目的:研究组蛋白H3K36三甲基转移酶SETD2对结肠直肠癌(CRC)细胞发生和生长的影响。方法:通过短发夹RNA转染降低CRC细胞系HCT116和SW480中SETD2的mRNA和蛋白质表达水平。检测转染后的CRC细胞系中三甲基化H3K36的蛋白质表达水平和肿瘤细胞增殖及迁移能力的变化,通过裸鼠成瘤实验观察KD组和对照组SETD2对于肿瘤生长的影响。结果:在CRC细胞中,随着SETD2的mRNA及蛋白质表达水平下降,检测到三甲基化H3K36蛋白质表达下降,且CRC细胞的增殖和迁移能力显著提升(P<0.05)。在裸鼠成瘤实验中通过免疫组织化学染色法,检测到KD组的小鼠肿瘤组织内三甲基化H3K36的蛋白质表达水平明显低于对照组。KD组裸鼠肿瘤的发生时间明显早于对照组,肿瘤的直径也明显大于对照组(P<0.01)。结论:下调SETD2的mRNA和蛋白质表达导致肿瘤组织三甲基化H3K36蛋白质表达下降,迁移和增殖能力增强,研究提示SETD2在CRC发生中的重要作用。

Objective To study the effect of histone H3 lysine 36 trimethyl transferase SETD2 on colorectal cancer(CRC)cells and the tumorigenesis.Methods The expression of SETD2 mRNA and protein decreased in CRC cell HCT116 and SW480 with transference of short hairpin RNA.There were KD group and control group.The expression of histone H3 proteins that are trimethylated on lysine 36(H3 K36 me3)was detected,and the migration and proliferation capacity of two CRC cell lines were examined.The effect of SETD2 on tumor growth were observed in nude mice experiment.Results The expression of H3 K36 me3 protein reduced in CRC cells following the decrease in expression of SETD2 mRNA and protein.The proliferation and migration in CRC cells increased significantly(P<0.05).H3 K36 me3 protein expression in tumor tissue of KD groups in nude mice experiment was much lower than that in control group by immunohistochemical staining.Tumorgenesis in KD groups occurred earlier and grew larger in size than those in control group(P<0.01).Conclusions Downregulation of SETD2 mRNA and protein expression in CRC cells would induce the decrease of H3 K36 me3 protein expression in tumor tissues with migration and proliferation of tumor cells increased which suggest that SETD2 plays an important role in pathogenesis of CRC.