miRNA-381改变CCNA2表达对乳腺癌增殖、迁移和预后的影响

Impacts of miRNA-381 on proliferation,migration and prognosis of breast cancer by altering CCNA2 expression

目的探讨miRNA-381通过改变细胞周期蛋白A2(CCNA2)的表达水平,对乳腺癌增殖、迁移和预后的影响。方法选择2017年6月至2018年6月于上海市静安区中心医院接受手术治疗的乳腺癌患者血清标本122例作为乳腺癌组。选择同期体检健康者血清标本75例作为对照组。采用实时荧光定量PCR(RT-PCR)检测各组血清和乳腺癌细胞系中miRNA-381和CCNA2的表达水平。结果乳腺癌组血清miRNA-381的表达水平明显低于对照组(1.71±0.64 vs 2.66±0.89,t=8.693,P<0.01),术后乳腺癌患者血清miRNA-381的表达水平较术前(2.46±0.76 vs 1.71±0.64,t=8.338,P<0.01)明显升高;而乳腺癌组血清CCNA2的表达水平较对照组(2.91±0.95 vs 2.33±0.73,t=4.528,P<0.01)明显升高,术后血清CCNA2的表达水平(2.42±0.63 vs 2.91±0.95,t=4.748,P<0.01)较术前明显降低。miRNA-381抑制乳腺癌细胞CCNA2基因和蛋白质的表达(P<0.01),且对乳腺癌细胞的增殖和迁移具有明显的抑制作用(P<0.01)。乳腺癌患者血清miRNA-381和CCNA2的表达水平在淋巴结转移与否、TNM分期和Ki67比率之间的差异具有统计学意义(P<0.01)。与死亡组比较,生存组血清miRNA-381的表达水平明显升高(P<0.01),而血清CCNA2的表达水平明显降低。血清miRNA-381和CCNA2的表达在预测乳腺癌患者术后3年内出现死亡时具有较高的预测效能,二者联合检测的敏感性为75.0%,特异性为84.7%,AUC^(ROC)为0.876,均显著高于miRNA-381(Z=1.993,P<0.05)和CCNA2(Z=2.539,P<0.05)单独检测。结论miRNA-381通过改变CCNA2的表达,影响乳腺癌细胞的增殖和迁移,血清miRNA-381和CCNA2在预测乳腺癌预后方面具有重要临床意义。

Objective To investigate the impacts of miRNA-381 on proliferation,migration and prognosis of breast cancer by altering the expression of cyclin A2(CCNA2).Methods A total of 122 serum samples from the patients with breast cancer who were treated surgically in Shanghai Jing′an District Central Hospital from June 2017 to June 2018 were selected as the breast cancer group,and 75 serum samples of healthy individuals in our hospital during the same period were selected as control group.The expressions of miRNA-381 and CCNA2 in serum and cells were detected by real-time fluorescent quantitative polymerase chain reaction(RT-PCR).Results The expression level of miRNA-381 in the serum of breast cancer group was significantly lower than that of the control group(1.71±0.64 vs 2.66±0.89,t=8.693,P<0.01),but after operation it was significantly higher than that before operation(2.46±0.76 vs 1.71±0.64,t=8.338,P<0.01).The expression of CCNA2 in the serum of breast cancer group was significantly higher than that in control group(2.91±0.95 vs 2.33±0.73,t=4.528,P<0.01),but after surgical operation it was significantly lower than that before operation(2.42±0.63 vs 2.91±0.95,t=4.748,P<0.01).The miRNA-381 inhibited the expression of CCNA2 gene and its protein in breast cancer cells(P<0.01),and significantly inhibited the proliferation and migration of breast cancer(P<0.01).The expression levels of miRNA-381 and CCNA2 in the serum of breast cancer group showed significantly different for lymph node metastasis,different TNM stage and Ki67 ratio(P<0.01).Compared with the death group,the miRNA-381 expression in serum of the survival group was significantly high(P<0.01),while the expression of CCNA2 was significantly low(P<0.01).The expression of miRNA-381 and CCNA2 in serum showed high diagnostic efficacy in predicting death of patients within 3 years after surgical operation.The sensitivity of combined detection of both miRNA-381 and CCNA2 was 75.0%,specificity was 84.7%and AUC^(ROC) was 0.876,which were all significantly higher than those of single detection of miRNA-381(Z=1.993,P<0.05)or CCNA2(Z=2.539,P<0.05).Conclusion miRNA-381 should show important effects on the proliferation and migration of breast cancer cells by altering the expression of CCNA2.The expressions of miRNA-381 and CCNA2 in serum have important clinical significance in predicting the prognosis of breast cancer.