胃癌肌管素相关蛋白3基因的表达及其调控机制

Expression of MTMR3 in gastric cancer and its regulatory mechanism

目的 探讨肌管素相关蛋白3（MTMR3）在胃癌中的表达及微RNA（miR）-181a对其的调控作用.方法 收集2009年4月至2010年12月本院手术切除的胃腺癌组织和癌旁组织标本50对,以及胃镜下活检同期在本科住院的非肿瘤患者的正常胃黏膜组织标本50例,通过实时定量聚合酶链反应检测上述标本中miR-181a和MTMR3的表达,分析胃癌中MTMR3和miR-181a的表达高低与患者性别、年龄、肿瘤部位、分化程度、淋巴结转移和肿瘤TNM分期之间的关系.采用双荧光素酶实验验证miR-181a对MTMR3的靶向作用.结果 MTMR3在癌组织[0.027（0.010,0.062）]和癌旁组织[0.038（0.021,0.078）]中表达差异无统计学意义（P=0.071）,但均低于正常组织[0.212（0.082,0.332）,均P＜0.05].miR-181a在癌组织[3.398（0.580,28.787）]、癌旁组织[0.502（0.100,4.504）]和正常组织[0.079（0.038,0.121）]中的表达依次降低（均P＜0.05）.胃癌组织miR-181a高表达者合并淋巴结转移几率高（P=0.042）,而MTMR3的表达则与患者的性别、年龄、肿瘤部位、分化程度、淋巴结转移和肿瘤TNM分期无显著关联.荧光素酶实验证实MTMR3为miR-181a的直接靶基因.结论 MTMR3在胃癌中表达下降,miR-181a的靶向抑制是其低表达的调控机制之一.

Objective To investigate the expression of myotubularin-related protein 3 （MTMR3） in gastric cancer （GC） and its regulatory mechanism by microRNA （miR）-181a.Methods A total of 50 pairs of gastric adenocarcinoma and para-carcinoma tissue specimens of patients,who underwent resection between April 2009 and December 2010,and 50 normal gastric mucosa tissue specimens of a contemporary cohort non-cancerous patients,who were hospitalized and underwent gastroscopic biopsy in Guangzhou First Municipal People＆#39;s Hospital,were included in the study.The expression levels of miR-181a and MTMR3 in the specimens were determined by real-time quantitative polymerase chain reaction.The correlation between the high/low expression levels of miR-181a and MTMR3 in GC and the gender,age,tumor location,tumor differentiation,lymph node metastasis and TNM tumor stage of patients were analyzed.The dual-luciferase assay was used to verify the targeting effect of miR-181a on MTMR3.Results MTMR3 expression levels in carcinoma tissues [0.027 （0.010,0.062）] and para-carcinoma tissues [0.038 （0.021,0.078）] had no statistically significant differences （P=0.071）,which were lower than that in normal tissues [0.212 （0.082,0.332）,all P〈0.05].The expression level of miR-18 1 a was highest in carcinoma tissues,followed by paracarcinoma tissues,and lowest in normal tissues [3.398 （0.580,28.787） vs 0.502 （0.100,4.504） vs 0.079 （0.038,0.121）,all P〈0.05].High risk of GC was found in the gastric cancer tissues with high expression of miR-181a and lymph node metastasis （P=0.042）.However,no significant associations were found between the expression of MTMR3 and the gender,age,tumor location,tumor differentiation,lymph node metastasis and TNM tumor stage of patients.Luciferase assay verified that MTMR3 was the direct target gene of miR-181a.Conclusion The expression of MTMR3 is decreased in GC,and the targeted inhibition of miR-181a is one of the regulatory mechanisms of its low expression.