Breast cancer is a complex, heterogeneous disease at the phenotypic and molecular level. In particular, the transcriptional regulatory programs are known to be significantly affected and such transcriptional alterations are able to capture some of the heterogeneity of the disease, leading to the emergence of breast cancer molecular subtypes. Recently, it has been found that network biology approaches to decipher such abnormal gene regulation programs, for instance by means of gene co-expression networks, have been able to recapitulate the differences between breast cancer subtypes providing elements to further understand their functional origins and consequences. Network biology approaches may be extended to include other co-expression patterns, like those found between genes and non-coding transcripts such as microRNAs (miRs). As is known, miRs play relevant roles in the establishment of normal and anomalous transcription processes. Commodore miRs (cdre-miRs) have been defined as miRs that, based on their connectivity and redundancy in co-expression networks, are potential control elements of biological functions. In this work, we reconstructed miR–gene co-expression networks for each breast cancer molecular subtype, from high throughput data in 424 samples from the Cancer Genome Atlas consortium. We identified cdre-miRs in three out of four molecular subtypes. We found that in each subtype, each cdre-miR was linked to a different set of associated genes, as well as a different set of associated biological functions. We used a systematic literature validation strategy, and identified that the associated biological functions to these cdre-miRs are hallmarks of cancer such as angiogenesis, cell adhesion, cell cycle and regulation of apoptosis. The relevance of such cdre-miRs as actionable molecular targets in breast cancer is still to be determined from functional studies.

乳腺癌在表型和分子水平上是一种复杂的异质性疾病。特别是，已知转录调控程序受到显着影响，并且这种转录改变能够捕捉到疾病的一些异质性，从而导致乳腺癌分子亚型的出现。最近，已经发现用于破译这种异常基因调控程序的网络生物学方法，例如通过基因共表达网络，能够概括乳腺癌亚型之间的差异，为进一步了解它们的功能起源和后果提供要素. 网络生物学方法可以扩展到包括其他共表达模式，例如在基因和非编码转录本（如 microRNA (miRs) 之间发现的模式）。众所周知，miR在建立正常和异常转录过程中发挥相关作用。Commodore miRs (cdre-miRs) 被定义为基于它们在共表达网络中的连接性和冗余性，是生物学功能的潜在控制元件的 miRs。在这项工作中，我们从癌症基因组图谱联盟的 424 个样本中的高通量数据重建了每种乳腺癌分子亚型的 miR-基因共表达网络。我们在四种分子亚型中的三种中鉴定了 cdre-miR。我们发现，在每个亚型中，每个 cdre-miR 都与一组不同的相关基因以及一组不同的相关生物学功能相关联。我们使用了系统的文献验证策略，并确定这些 cdre-miR 的相关生物学功能是癌症的标志，如血管生成、细胞粘附、细胞周期和细胞凋亡的调节。此类 cdre-miRs 作为乳腺癌中可操作分子靶标的相关性仍有待从功能研究中确定。