高度转录非编码元件（HTNEs）是具有高水平转录能力的关键非编码元件，涉及到多种细胞生物学过程的特定群体。研究在异常组织中持续异常表达的HTNEs可能有助于探索它们在疾病发生和进展中的作用。乳腺癌是一种高度异质性的疾病，早期筛查和预后非常重要。在本研究中，我们开发了一个HTNE鉴定框架，系统研究乳腺癌患者中的HTNE景观，并鉴定了一万多个HTNEs。通过公共数据集验证了我们框架的稳健性和合理性。我们发现，HTNEs具有明显的染色质增强子和长链非编码RNA（lncRNA）的特征，并且明显富集于RNA结合蛋白，同时也成为miRNA的靶点。此外，HTNE相关基因显著过表达，并且与乳腺癌呈强相关。最终，我们探究了与HTNEs相关的亚型特定转录过程，并揭示了能够基于激素受体特性对乳腺癌亚型分类的HTNE标志。我们的结果强调，所鉴定的HTNEs及其相关基因在乳腺癌进展中起着关键作用，并与乳腺癌的亚型特定转录过程相关。© 2023 The Authors.

Highly transcribed noncoding elements (HTNEs) are critical noncoding elements with high levels of transcriptional capacity in particular cohorts involved in multiple cellular biological processes. Investigation of HTNEs with persistent aberrant expression in abnormal tissues could be of benefit in exploring their roles in disease occurrence and progression. Breast cancer is a highly heterogeneous disease for which early screening and prognosis are exceedingly crucial. In this study, we developed a HTNE identification framework to systematically investigate HTNE landscapes in breast cancer patients and identified over ten thousand HTNEs. The robustness and rationality of our framework were demonstrated via public datasets. We revealed that HTNEs had significant chromatin characteristics of enhancers and long noncoding RNAs (lncRNAs) and were significantly enriched with RNA-binding proteins as well as targeted by miRNAs. Further, HTNE-associated genes were significantly overexpressed and exhibited strong correlations with breast cancer. Ultimately, we explored the subtype-specific transcriptional processes associated with HTNEs and uncovered the HTNE signatures that could classify breast cancer subtypes based on the properties of hormone receptors. Our results highlight that the identified HTNEs as well as their associated genes play crucial roles in breast cancer progression and correlate with subtype-specific transcriptional processes of breast cancer.© 2023 The Authors.