Petrović Nina
Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, 11000, Belgrade, Serbia.
Mol Diagn Ther. 2016 Apr;20(2):97-110. doi: 10.1007/s40291-016-0186-3.
Breast cancer (BC) is a heterogeneous disease that develops into a large number of varied phenotypes. One of the features used in its classification and therapy selection is invasiveness. MicroRNA-21 (miR-21) is considered to be an important element of BC invasiveness, and miR-21 levels are frequently increased in different tumor types compared with normal tissue, including the breast. Experimental and literature research has highlighted that miR-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. The main goal of this research was to specify the predominant role of miR-21 in the different phases of BC pathogenesis, i.e. whether it was involved in the early (initiation), later (promotion), or late (propagation, progression) phases. Our second goal was to explain the roles of miR-21 targets in BC by an in silico approach and literature review, and to associate the importance of miR-21 with particular phases of BC pathogenesis through the action of its target genes. Analysis has shown that changes in miR-21 levels might be important for the later and/or late phases of breast cancerogenesis rather than for the initial early phases. Targets of miR-21 (TIMP3, PDCD4, PTEN, TPM1 and RECK) are also primarily involved in BC promotion and progression, especially invasion, angiogenesis and metastasis. miR-21 expression levels could perhaps be used in conjunction with the standard diagnostic parameters as an indicator of BC presence, and to indicate a phenotype likely to show early invasion/metastasis detection and poor prognosis.
乳腺癌(BC)是一种异质性疾病,会发展成多种不同的表型。其分类和治疗选择所依据的特征之一是侵袭性。微小RNA-21(miR-21)被认为是BC侵袭性的一个重要因素,与包括乳腺在内的正常组织相比,miR-21水平在不同肿瘤类型中常常升高。实验和文献研究表明,在每一项纳入浸润性乳腺癌的研究中,与健康乳腺组织相比,miR-21总是显著升高。本研究的主要目的是明确miR-21在BC发病机制不同阶段的主要作用,即它是否参与早期(起始)、中期(促进)或晚期(增殖、进展)阶段。我们的第二个目的是通过计算机模拟方法和文献综述来解释miR-21靶点在BC中的作用,并通过其靶基因的作用将miR-21的重要性与BC发病机制的特定阶段联系起来。分析表明,miR-21水平的变化可能对乳腺癌发生的中期和/或晚期很重要,而不是对最初的早期阶段。miR-21的靶点(TIMP3、PDCD4、PTEN、TPM1和RECK)也主要参与BC的促进和进展,特别是侵袭、血管生成和转移。miR-21表达水平或许可以与标准诊断参数结合使用,作为BC存在的指标,并表明一种可能显示早期侵袭/转移检测和预后不良的表型。