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乳腺纤维瘤和乳腺癌中的MTUS1肿瘤抑制因子及其miRNA调控因子

MTUS1 tumor suppressor and its miRNA regulators in fibroadenoma and breast cancer.

作者信息

Kara Murat, Kaplan Mehmet, Bozgeyik Ibrahim, Ozcan Onder, Celik Ozgur Ilhan, Bozgeyik Esra, Yumrutas Onder

机构信息

Mugla Sitki Kocman University, Faculty of Medicine, Department of Medical Genetics, Mugla, Turkey.

Bahcesehir University, School of Medicine, Department of General Surgery, Istanbul, Turkey.

出版信息

Gene. 2016 Aug 10;587(2):173-7. doi: 10.1016/j.gene.2016.05.006. Epub 2016 May 4.

Abstract

Breast cancer is major public health problem predominantly effects female population. Current therapeutic approaches to deal with breast cancer are still lack of effectiveness. Thus, identifying/developing novel strategies to fight against breast cancer is very important. The frequent deletions at 8p21.3-22 chromosomal location nearby D8S254 marker enabled the discovery of a novel tumor suppressor gene, MTUS1. Subsequently, MTUS1 was demonstrated to be less expressed in a variety cancer types including breast cancer. Also, it is obvious that gene expression is widely regulated by miRNAs. Here, we aimed to report differential expression of MTUS1 and its regulatory miRNAs in breast cancer and fibroadenoma tissues. Dynamic analysis of MTUS1 expression levels and its miRNAs regulators were attained by Fluidigm 96×96 Dynamic Array Expression chips and reactions were performed in Fluidigm BioMark™ HD System qPCR. Consequently, MTUS1 mRNA levels were significantly diminished in breast cancer tissues and elevated in fibroadenoma tissues. Also, among MTUS1 targeting miRNAs, miR-183-5p was identified to be overexpressed in breast cancer and down-regulated in fibroadenoma tissues. Also, expression levels of MTUS1 and miR-183-5p were well correlated with clinical parameters. In particular, MTUS1 expression was found to be diminished and miR-183-5p expression was elevated with the advancing stage. In conclusion, as a potential therapeutic target, miR-183-5p can be a chief regulator of MTUS1 and MTUS1-miR-183-5p axis may have significant influence in the pathology of breast cancer.

摘要

乳腺癌是一个主要的公共卫生问题,主要影响女性人群。目前治疗乳腺癌的方法仍然缺乏有效性。因此,识别/开发对抗乳腺癌的新策略非常重要。在靠近D8S254标记的8p21.3 - 22染色体位置频繁出现的缺失,促成了一种新型肿瘤抑制基因MTUS1的发现。随后,MTUS1被证明在包括乳腺癌在内的多种癌症类型中表达较低。此外,基因表达显然受到微小RNA(miRNA)的广泛调控。在此,我们旨在报告MTUS1及其调控性miRNA在乳腺癌和纤维腺瘤组织中的差异表达。通过Fluidigm 96×96动态阵列表达芯片实现对MTUS1表达水平及其miRNA调控因子的动态分析,并在Fluidigm BioMark™ HD系统定量聚合酶链反应(qPCR)中进行反应。结果,MTUS1信使核糖核酸(mRNA)水平在乳腺癌组织中显著降低,而在纤维腺瘤组织中升高。此外,在靶向MTUS1的miRNA中,miR - 183 - 5p被确定在乳腺癌中过表达,而在纤维腺瘤组织中下调。此外,MTUS1和miR - 183 - 5p的表达水平与临床参数密切相关。特别是,随着疾病进展,发现MTUS1表达降低,而miR - 183 - 5p表达升高。总之,作为一个潜在的治疗靶点,miR - 183 - 5p可能是MTUS1的主要调节因子,并且MTUS1 - miR - 183 - 5p轴可能在乳腺癌的病理过程中具有重要影响。

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