MicroRNA-487b-3p Represses Cell Functions and Epithelial-Mesenchymal Transition and Acts as a Prognostic Predictor for Breast Cancer

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yang Wang, Jianhong Liu, Haizhen Yu, Shizhen Li, Wenyan Wang
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引用次数: 0

Abstract

Our aim was to ascertain the clinical implications of microRNA-487b-3p (miR-487b-3p) in breast cancer. MiR-487b-3p level was measured in breast cancer tissues (n = 102) and adjacent noncancerous tissues (n = 102) using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier method and Cox regression analysis were conducted for evaluating the clinical performance of miR-487b-3p. Cell counting kit-8 (CCK-8) and Transwell assay were utilized for cellular functions. Bioinformatics tools and luciferase reporter assay were performed for the target predication and confirmation. MiR-487b-3p was remarkably diminished in breast cancer tissues. Aberrant miR-487b-3p was tightly in relation to Ki67 (p = 0.003), human epidermal growth factor receptor (HER2) status (p = 0.025), tumor node metastasis (TNM) stage (p = 0.028) and lymph node metastasis (p = 0.002). Moreover, a better progression free survival rate was found in patients expressing high miR-487b-3p (n = 51, p < 0.001) than those with low expression (n = 51). Additionally, miR-487b-3p was an independent predictor for the prognosis of breast cancer (p < 0.001; HR = 2.971; 95% CI = 1.721–5.131). Enforced miR-487b-3p expression obviously restrained cell activities and epithelial-mesenchymal transition (EMT), while apposite effects were observed posttransfection with miR-487b-3p inhibitor (p < 0.001). Notably, low-density lipoprotein receptor-related protein 6 (LRP6) was a potential target gene of miR-487b-3p, an adverse relevance of which was discovered (r = −0.5811; p < 0.001). MiR-487b-3p was an underlying indicator for the prognosis in breast cancer. It impacted on cell activities and EMT via regulating LRP6 in breast cancer development.

Clinical trial registration: Not applicable.

MicroRNA-487b-3p抑制细胞功能和上皮-间质转化并作为乳腺癌的预后预测因子
我们的目的是确定microRNA-487b-3p (miR-487b-3p)在乳腺癌中的临床意义。采用实时荧光定量聚合酶链式反应(qRT-PCR)检测乳腺癌组织(n = 102)和癌旁非癌组织(n = 102)中MiR-487b-3p水平。采用Kaplan-Meier法和Cox回归分析评价miR-487b-3p的临床表现。细胞计数试剂盒-8 (CCK-8)和Transwell法检测细胞功能。生物信息学工具和荧光素酶报告基因检测用于预测和确认靶标。MiR-487b-3p在乳腺癌组织中明显减少。miR-487b-3p异常与Ki67 (p = 0.003)、人表皮生长因子受体(HER2)状态(p = 0.025)、肿瘤淋巴结转移(TNM)分期(p = 0.028)和淋巴结转移(p = 0.002)密切相关。此外,miR-487b-3p高表达的患者(n = 51, p < 0.001)比低表达的患者(n = 51)有更好的无进展生存率。此外,miR-487b-3p是乳腺癌预后的独立预测因子(p < 0.001;hr = 2.971;95% ci = 1.721-5.131)。强化miR-487b-3p表达明显抑制细胞活性和上皮-间质转化(EMT),而转染miR-487b-3p抑制剂后观察到相反的效果(p < 0.001)。值得注意的是,低密度脂蛋白受体相关蛋白6 (LRP6)是miR-487b-3p的潜在靶基因,两者之间存在负相关(r = - 0.5811;p < 0.001)。MiR-487b-3p是乳腺癌预后的潜在指标。它通过调节乳腺癌发展中的LRP6影响细胞活性和EMT。临床试验注册:不适用。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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