Dai Wenzhu, He Jixiang, Zheng Ling, Bi Mingyu, Hu Fei, Chen Minju, Niu Heng, Yang Jingyu, Luo Ying, Tang Wenru, Sheng Miaomiao
Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Yunnan, China.
Department of Mammary Gland and Thyroid Disease, First People's Hospital of Yunnan Province, Yunnan, China.
J Breast Cancer. 2019 Jun;22(2):219-236. doi: 10.4048/jbc.2019.22.e19.
Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer.
We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool.
A total of 68 miRNAs showed significantly different expression patterns between the groups ( < 0.001), and 13 of these miRNAs were significantly associated with poor survival ( < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways.
The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.
乳腺癌是全球女性中最常被诊断出的恶性肿瘤。微小RNA(miRNA)被认为是包括乳腺癌在内的各种癌症的潜在生物标志物。
我们评估了来自癌症基因组图谱数据库的1083例乳腺癌样本和104例正常乳腺组织中的miRNA表达谱。我们使用R软件的edgeR包分析正常组织和癌组织中差异表达的miRNA,并通过Kaplan-Meier分析筛选与生存相关的miRNA。生成受试者工作特征曲线以评估这些miRNA作为乳腺癌诊断分子标志物的准确性。此外,使用细胞实验验证了这些miRNA的功能作用。使用9个在线数据库预测候选miRNA的靶标,并使用在线注释、可视化和综合发现数据库工具进行基因本体(GO)功能注释和通路分析。
共有68种miRNA在两组之间表现出显著不同的表达模式(<0.001),其中13种miRNA与不良生存显著相关(<0.05)。选择了三种具有高特异性和敏感性的miRNA,即miR-148b-3p、miR-190b和miR-429。实验表明,这三种miRNA的过表达显著促进了MDA-MB-468和T47D细胞的增殖和迁移,并减少了T47D细胞的凋亡。GO和通路富集分析表明,这些失调miRNA的靶标参与了许多关键的癌症相关生物学过程和通路。
miR-148b-3p、miR-190b和miR-429可能作为乳腺癌的潜在诊断和预后标志物。本研究证明了这三种miRNA在乳腺癌发生和发展中的作用。