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miR-142-3p及其靶基因HMGA1和FZD7在乳腺癌中的异常表达及其临床意义

Aberrant Expression of miR-142-3p and its Target Gene HMGA1 and FZD7 in Breast Cancer and its Clinical Significance.

作者信息

Jia Xiu-Peng, Meng Ling-Li, Fang Jian-Chen, Wang Hong-Wei, Chen Jie, Zhou Jue, Wang Chun-Nian, Jiang Wei-Feng

出版信息

Clin Lab. 2018 Jun 1;64(6):915-921. doi: 10.7754/Clin.Lab.2017.171114.

Abstract

BACKGROUND

Breast cancer is the second leading cause of cancer-related death among women worldwide. The aim of this study is to investigate the role of miR-142-3p in breast cancer cells and the related mechanism.

METHODS

Sixty paired breast cancer tissues were collected and 60 breast tissues from patients with mammary hyperplasia served as the control group. The expression of miR-142-3p was examined using RT-qPCR methods; moreover, we also performed receiver operating characteristic (ROC) curve analysis to determine whether miR142-3p can distinguish breast cancer patients from the controls. Next, HMGA1 and FZD7 have been predicted as target genes of miR-142-3p, and the expressions of HMGA1 and FZD7 in breast cancer tissue and the control group were examined using RT-qPCR and western blot methods.

RESULTS

miR-142-3p was significantly down-regulated in breast cancer tissue compared with the controls, and the levels of miR-142-3p was negatively correlated with the tumor size, degree of differentiation, and metastasis (p < 0.01). Moreover, results of ROC curve analysis indicated that the expression of miR-142-3p can distinguish between patients with breast cancer and the control group (AUC = 0.819, 95% CI, 0.756 - 0.881). Furthermore, the expressions of HMGA1 and FZD7 were significantly up-regulated in patients with breast cancer compared with the controls. The level of miR-142-3p was negatively correlated with expressions of HMGA1 (r = -0.3507, p = 0.006) and FZD7 (r = -0.3410, p = 0.0077) in patients with breast cancer.

CONCLUSIONS

Our results proved that miR-142-3p may serve as a tumor suppressor in breast cancer by suppressing the expression of oncogene HMGA1 and FZD7, suggesting that miR-142-3p has the potential to become a diagnostic marker and therapeutic target for the early diagnosis and treatment of breast cancer.

摘要

背景

乳腺癌是全球女性癌症相关死亡的第二大主要原因。本研究的目的是探讨miR-142-3p在乳腺癌细胞中的作用及其相关机制。

方法

收集60对乳腺癌组织,并将60例乳腺增生患者的乳腺组织作为对照组。采用RT-qPCR方法检测miR-142-3p的表达;此外,我们还进行了受试者工作特征(ROC)曲线分析,以确定miR-142-3p是否能够区分乳腺癌患者和对照组。接下来,HMGA1和FZD7已被预测为miR-142-3p的靶基因,并采用RT-qPCR和蛋白质印迹法检测HMGA1和FZD7在乳腺癌组织和对照组中的表达。

结果

与对照组相比,miR-142-3p在乳腺癌组织中显著下调,且miR-142-3p的水平与肿瘤大小、分化程度和转移呈负相关(p < 0.01)。此外,ROC曲线分析结果表明,miR-142-3p的表达能够区分乳腺癌患者和对照组(AUC = 0.819,95% CI,0.756 - 0.881)。此外,与对照组相比,乳腺癌患者中HMGA1和FZD7的表达显著上调。在乳腺癌患者中,miR-142-3p的水平与HMGA1(r = -0.3507,p = 0.006)和FZD7(r = -0.3410,p = 0.0077)的表达呈负相关。

结论

我们的结果证明,miR-142-3p可能通过抑制癌基因HMGA1和FZD7的表达而作为乳腺癌中的肿瘤抑制因子,这表明miR-142-3p有潜力成为乳腺癌早期诊断和治疗的诊断标志物和治疗靶点。

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