Pinto R, De Summa S, Danza K, Popescu O, Paradiso A, Micale L, Merla G, Palumbo O, Carella M, Tommasi S
IRCCS 'Giovanni Paolo II', Molecular Genetics Laboratory, Viale Orazio Flacco 65, Bari 70124, Italy.
IRCCS 'Giovanni Paolo II', Anatomopathology Unit, Bari, Italy.
Br J Cancer. 2014 Dec 9;111(12):2361-8. doi: 10.1038/bjc.2014.535. Epub 2014 Nov 13.
Gender-associated epigenetic alterations are poorly investigated in male and female familial breast cancer (fBC). MicroRNAs may contribute to the different biology in men and women particularly related to RASSF1A pathways.
Microarray technology was used to evaluate miRNA profile in 24 male and 43 female fBC. Key results were validated using RT-qPCR in an external samples set. In vitro studies were carried out to verify microRNA-target gene interaction.
Pathway enrichment analysis with the 287 differentially expressed microRNAs revealed several signalling pathways differently regulated in male and female cases. Because we previously hypothesised a peculiar involvement of RASSF1A in male fBC pathogenesis, we focussed on the MAPK and the Hippo signalling pathways that are regulated by RASSF1A. Male miR-152 and miR-497 upregulation and RASSF1A and NORE1A interacting gene downregulation were observed, confirming a possible indirect interaction between miRNAs and the two genes.
For the first time, a different microRNA expression pattern in male and female fBC has been shown. Moreover, the importance of RASSF1A pathway in male fBC carcinogenesis has been confirmed, highlighting a possible role for miR-152 and miR-497 in controlling MAPK and Hippo signalling pathways, regulated by RASSF1A.
在男性和女性家族性乳腺癌（fBC）中，与性别相关的表观遗传改变研究较少。微小RNA可能导致男性和女性生物学差异，特别是与RASSF1A通路相关。
利用微阵列技术评估24例男性和43例女性fBC中的miRNA谱。在外部样本集中使用RT-qPCR验证关键结果。进行体外研究以验证微小RNA-靶基因相互作用。
对287种差异表达的微小RNA进行通路富集分析，发现男性和女性病例中几种信号通路的调控方式不同。由于我们之前假设RASSF1A在男性fBC发病机制中具有特殊作用，我们重点关注由RASSF1A调控的MAPK和Hippo信号通路。观察到男性miR-152和miR-497上调以及RASSF1A和NORE1A相互作用基因下调，证实了微小RNA与这两个基因之间可能存在间接相互作用。
首次显示了男性和女性fBC中不同的微小RNA表达模式。此外，RASSF1A通路在男性fBC致癌作用中的重要性得到证实，突出了miR-152和miR-497在控制由RASSF1A调控的MAPK和Hippo信号通路中的可能作用。
