miR-222、MBD2在胃癌患者中的表达及对铂类化疗敏感性的影响

目的:研究miRNA-222与甲基化CpG结合结构蛋白2（MBD2）水平在胃癌组织中的表达水平及其对铂类化疗敏感性的影响。方法:选择2016年2月至2017年5月在本院就诊的75例原发性胃癌患者作为研究对象。检测患者癌组织及癌旁组织中miR-222、MBD2表达水平；分析miR-222、MBD2水平与胃癌临床病理参数的相关性。将miR-222 inhibitor转染至胃癌SGC-7901细胞中，RT-PCR和Western blot分别检测转染后细胞中miR-222和MBD2的表达水平，MTT法、流式细胞术分别检测转染对细胞增殖、凋亡的影响。结果:胃癌组织中miR-222的阳性表达率显著高于癌旁组织（P<0.05）。胃癌组织中miR-222相对表达量显著高于癌旁组织（P<0.05）。胃癌组织中MBD2的阳性表达率显著低于癌旁组织（P<0.05）。miR-222及MBD2表达水平与分化程度、TNM分期有明显相关性（P<0.05）。转染miR-222 inhibitor的各组SGC-7901细胞中miR-222表达水平均显著低于空白对照组（Control组）和miR-NC组（NC组）（P<0.05）。转染miR-222 inhibitor的各组细胞中MBD2 mRNA和蛋白表达水平显著高于Control组和NC组（P<0.05）。转染miR-222 inhibitor的各组细胞的增殖率显著低于Control组和NC组（P<0.05），且miR-222 inhibitor+顺铂（Cisplatin，CDDP ）组的细胞增殖率显著低于miR-222 inhibitor组及CDDP 组，细胞凋亡率显著高于miR-222 inhibitor组及CDDP 组（P<0.05），且与CDDP联合运用能够更明显地抑制肿瘤细胞的增殖率，促进细胞的凋亡。结论:miR-222在胃癌组织中表达明显上调，MBD2显著下调，其表达高低与胃癌分化程度、TNM分期有明显相关性。miR-222可增强 CDDP 对胃癌的化疗敏感性，其可能通过抑制胃癌中的靶基因MBD2发挥作用。

Expression of miR-222 and MBD2 in gastric cancer patients and their effects on platinum chemosensitivity

AIM: To study the expression level of miRNA-222 and methylated CpG binding structural protein 2 (MBD2) in gastric cancer and its effect on proliferation and apoptosis of human gastric cancer cells. METHODS:Seventy-five patients with primary gastric cancer who were admitted to our hospital from February 2016 to May 2017 were selected as subjects. The expression levels of miR-222 and MBD2 in cancer tissues and adjacent tissues were detected. The correlation between miR-222 and MBD2 levels and clinicopathological parameters of gastric cancer were analyzed. The miR-222 inhibitor was transfected into gastric cancer SGC-7901 cells. The expression levels of miR-222 and MBD2 were detected by RT-PCR and Western blot, respectively. MTT assay and flow cytometry were used to detect. The effects of transfected cells on proliferation and apoptosis. RESULTS:The positive expression rate of miR-222 in gastric cancer tissues was significantly higher than that in adjacent tissues (P<0.05). The relative expression of miR-222 in gastric cancer tissues was significantly higher than that in adjacent tissues (P<0.05). The positive expression rate of MBD2 in gastric cancer tissues was significantly lower than that in adjacent tissues (P<0.05). The expression levels of miR-222 and MBD2 were significantly correlated with the degree of differentiation and TNM stage (P<0.05). The expression level of miR-222 in SGC-7901 cells transfected with miR-222 inhibitor was significantly lower than that in control group and NC group (P<0.05). The expression levels of MBD2 mRNA and protein in the cells transfected with miR-222 inhibitor were significantly higher than those in control group and NC group (P<0.05). The proliferation rate of cells transfected with miR-222 inhibitor was significantly lower than that of Control group and NC group (P<0.05), and the cell proliferation rate of miR-222 inhibitor+CDDP group was significantly lower than that of miR-222 inhibitor group and CDDP group. The apoptosis rate was significantly higher than that of miR-222 inhibitor group and CDDP group (P<0.05), and combined with CDDP could inhibit the proliferation rate of tumor cells and promote cell apoptosis. CONCLUSION: The expression of miR-222 in gastric cancer tissues is up-regulated in advanced gastric cancer tissues, and MBD2 is down-regulated significantly. The expression level of miR-222 is significantly correlated with the differentiation degree of gastric cancer and TNM stage. miR-222 can enhance the chemosensitivity of CDDP to gastric cancer，which may play a role in inhibiting the target gene MBD2 in gastric cancer.