Ahmadinejad Fereshteh, Mowla Seyed Javad, Honardoost Mohammad-Amin, Arjenaki Mostafa Gholami, Moazeni-Bistgani Mohammad, Kheiri Soleyman, Teimori Hossein
1 Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
2 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Tumour Biol. 2017 Aug;39(8):1010428317698362. doi: 10.1177/1010428317698362.
Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways.
乳腺癌被认为是全球女性中最常见的恶性肿瘤。尽管出现了多种用于更好管理患者的预后指标，但由于乳腺肿瘤的复杂性，它们在临床应用中仍存在局限性，因此，寻找新的生物标志物以更好地预测临床结局至关重要。微小RNA是高度保守的小非编码调节RNA，参与不同细胞机制中基因表达的转录后调控。越来越多的研究表明，miR-218在各种癌症类型和不同阶段发挥着多功能作用。在此，为了探讨miR-218在乳腺癌中的预后意义，我们使用定量实时聚合酶链反应，针对33对乳腺肿瘤及其相邻正常组织，研究了miR-218和B细胞特异性莫洛尼鼠白血病病毒整合位点1（BMI1）基因（作为miR-218的假定靶标之一）的表达谱，并分析了患者的临床病理特征。我们还通过OncoLNC数据门户，研究了miR-218和BMI1基因表达与乳腺癌患者总生存期的相关性。最后，为了更好地了解miR-218在乳腺癌中的生物学功能，我们对miR-218靶标组进行了计算机基因本体论和信号通路富集分析。根据我们的数据，与正常组织相比，临床乳腺癌标本中miR-218表达显著升高，BMI1表达下调（p < 0.0001）。miR-218表达较低与淋巴结转移、更高分级和更差预后相关（对数秩检验p = 0.00988），而BMI1表达较高和较低的患者之间总生存期无显著差异（对数秩检验p = 0.254）。这些发现表明，miR-218表达谱可能在临床上作为乳腺癌的预后生物标志物应用。此外，我们的计算机富集分析表明，miR-218表达与乳腺癌预后的关联可能是通过其参与内吞作用和间隙连接生物途径实现的。
