长链非编码RNA X染色体失活特异转录物调控微小RNA-335对胃癌的增殖和迁移的影响

Long non-coding RNA X-inactive specific transcript regulates microRNA-335 to affect the proliferation and migration of gastric cancer

目的探讨长链非编码RNA(lncRNA)X染色体失活特异转录物(XIST)对胃癌细胞增殖、迁移的影响及其作用机制。方法收集2018年1月至2019年12月来自宜昌市中心人民医院的胃癌患者42例,采用定量聚合酶链反应(qPCR)检测XIST在胃癌患者肿瘤组织和癌旁正常组织中表达,分析XIST表达与患者临床病理参数的相关性。采用qPCR检测XIST在胃癌细胞系中的表达,通过转染小干扰RNA(si-XIST)敲低XIST在胃癌细胞SGC-7901和AGS中的表达,分别将胃癌细胞分为si-XIST组和si-NC组,细胞计数试剂盒(CCK-8)检测各组细胞的增殖活性,细胞划痕实验和Transwell法检测细胞迁移和侵袭能力,双荧光素酶验证XIST与微小RNA(miR)-335的靶向关系。组间比较采用t检验。结果XIST在胃癌组织中相对表达量为1.86±0.24,显著高于癌旁正常组织的0.98±0.11,差异有统计学意义(P<0.05),同样,胃癌细胞系中XIST的相对表达显著上调(P<0.05),差异有统计学意义。组织样本中XIST的表达与患者的TNM分期和淋巴结转移明显相关(P<0.05),差异有统计学意义,敲低XIST表达可显著降低胃癌细胞的增殖、迁移和侵袭能力,XIST可负向调控miR-335的表达。结论lncRNA XIST可负向调控miR-335的表达,从而抑制胃癌的增殖、迁移和侵袭能力。

Objective To investigate the effect of long non-coding RNA(lncRNA)X-inactive specific transcript(XIST)on the proliferation and migration of gastric cancer cells and its underlying mechanism.Methods Totslly 42 cases of gastric cancer from Yichang Central People′s Hospital were collected from January 2018 to December 2019.Quantitative polymerase chain reaction(qPCR)was used to detect the expression of XIST in tumor tissues and adjacent normal tissues of gastric cancer patients,and the relationship between expression level and clinicopathological parameters was analyzed.The expression of XIST in gastric cancer cell lines was detected by qPCR,and si-XIST was used to knock down the expression of XIST in gastric cancer cells SGC-7901 and AGS,and gastric cancer cells were divided into si-XIST group and si-NC group.Cell counting kit-8(CCK-8)assay was performed to detect the proliferation activity.Cell scratch test and Transwell method were used to evaluate the cell migration and invasion ability.The targeted relationship between XIST and microRNA(miRNA,miR)-335 was verified by dual luciferase assay.The comparison between groups was performed by t test.Results The relative expression of XIST in gastric cancer tissues was 1.86±0.24,which was significantly higher than 0.98±0.11 in adjacent normal tissues(P<0.05).The relative expression of XIST in gastric cancer cell lines was significantly up-regulated(P<0.05).The expression of XIST in tumor tissues was significantly correlated with the TNM stage and lymph node metastasis(P<0.05).The proliferation,migration and invasion abilities of gastric cancer cells were significantly reduced after XIST was knocked down.Further experiments demonstrated that knockdown of XIST up-regulated the expression of miR-335.Conclusion LncRNA XIST promotes the proliferation,migration and invasion of gastric cancer cells by regulating miR335 expression.