microRNA-21、PTEN、RASA1及caspase-3在肾上腺醛固酮瘤中的表达及相关作用机制

Expression and mechanism of microRNA-21,PTEN,RASA1 and caspase-3 in adrenal aldosteronoma

目的研究microRNA-21(miR-21)、PTEN、RASA1及caspase-3在肾上腺醛固酮瘤中的表达情况,探究其内在相关性及对疾病的影响机制。方法采用荧光定量PCR法和免疫组织化学法检测样本中miR-21及PTEN、RASA1、caspase-3的表达量,再用细胞转染建立人肾上腺皮质细胞(HACC)模型,采用Western Blot技术检测细胞模型中caspase-3表达量。结果miR-21在肾上腺醛固酮瘤和瘤旁组织中的表达量分别为0.109±0.050和0.040±0.019,差异有统计学意义(P<0.001);其中瘤组织样本中PTEN阳性表达率为22.91%(P=0.001),瘤旁组织样本中PTEN阳性表达率85.42%(P=0.001),RASA1阳性表达率分别为8.33%和60.41%(P<0.001),caspase-3阳性表达率分别为25.00%和89.58%(P<0.001),均差异有统计学意义。HACC细胞模型显示,当miR-21过表达时,caspase-3蛋白表达下调,细胞表现出过度增殖趋势;miR-21表达抑制时,caspase-3蛋白表达上调,细胞表现为生长抑制。结论肾上腺醛固瘤组织中miR-21高表达可能通过下调PTEN、RASA1及caspase-3,从而抑制细胞凋亡并参与肿瘤进展。

Objective To investigate expressions of microRNA-21(miR-21),PTEN,RASA1 and caspase-3 in adrenal aldosteronoma and explore the internal correlation and the mechanism of its influence on the disease.MethodsThe expression of miR-21,PTEN,rasa1 and caspase-3 were detected by fluorescence quantitative PCR and immunohistochemistry respectively.HACC cell model was established by cell transfection,and caspase-3 expression was detected by Western Blot.Results The expression of miR-21 in adrenal aldosterone tumor and its adjacent tissues was 0.109±0.050 and 0.040±0.019,respectively(P<0.001).The positive expression rate of PTEN in tumor tissue and adjacent tissue was 22.91%and 85.42%,respectively(P=0.001).The positive expression rate of RASA1 in tumor tissue and adjacent tissue was 8.33%and 60.41%,respectively(P<0.001).The positive expression rate of caspase-3 in tumor tissue and adjacent tissue was 25.00%and 89.58%,respectively(P<0.001).The above data had significant differences.HACC cell model showed that when miR-21 was over expressed,caspase-3 protein expression was down regulated,and the cell showed an over proliferation trend;when miR-21 was down regulated,caspase-3 protein expression was down regulated,and the cell showed growth inhibition.Conclusion The high expression of miR-21 in adrenal aldehyde solid tumor tissue may be involved in tumor progression by down regulating PTEN,RASA1 and caspase-3.