As with other non-coding RNAs (ncRNAs), the aberrant expression of long non-coding RNAs (lncRNAs) can be associated with different forms of cancers, including breast cancer (BC). Various lncRNAs may either promote or suppress cell proliferation, metastasis, and other related cancer signaling pathways by interacting with other cellular machinery, thus affecting the expression of BC-related genes. However, lncRNAs are characterized by features that are unlike protein-coding genes, which pose unique challenges when it comes to their study and utility. They are highly diverse and may display contradictory functions depending on factors like the BC subtype, isoform diversity, epigenetic regulation, subcellular localization, interactions with various molecular partners, and the tumor microenvironment (TME), which contributes to the intratumoral heterogeneity and phenotypic plasticity. While lncRNAs have potential clinical utility, their functional heterogeneity coupled with a current paucity of knowledge of their functions present challenges for clinical translation. Strategies to address this heterogeneity include improving classification systems, employing CRISPR/Cas tools for functional studies, utilizing single-cell and spatial sequencing technologies, and prioritizing robust targets for therapeutic development. A comprehensive understanding of the lncRNA functional heterogeneity and context-dependent behavior is crucial for advancing BC research and precision medicine. This review discusses the sources of lncRNA heterogeneity, their implications in BC biology, and approaches to resolve knowledge gaps in order to harness lncRNAs for clinical applications.
与其他非编码RNA（ncRNA）类似，长链非编码RNA（lncRNA）的表达异常也与多种癌症相关，包括乳腺癌（BC）。不同的lncRNA可通过与细胞机制相互作用，促进或抑制细胞增殖、转移及其他相关癌症信号通路，从而影响乳腺癌相关基因的表达。然而，lncRNA具有与蛋白质编码基因不同的特征，这为其研究和应用带来了独特挑战。它们具有高度多样性，其功能可能因乳腺癌亚型、异构体多样性、表观遗传调控、亚细胞定位、与不同分子伴侣的相互作用以及肿瘤微环境（TME）等因素而呈现矛盾性，这些因素共同导致肿瘤内异质性和表型可塑性。尽管lncRNA具有临床应用的潜力，但其功能异质性及当前对其功能认知的不足，为临床转化带来了挑战。应对这种异质性的策略包括改进分类系统、利用CRISPR/Cas工具进行功能研究、采用单细胞和空间测序技术，以及优先选择稳健靶点进行疗法开发。全面理解lncRNA的功能异质性和环境依赖性行为，对于推进乳腺癌研究和精准医学至关重要。本综述探讨了lncRNA异质性的来源、其在乳腺癌生物学中的意义，以及填补知识空白的方法，旨在推动lncRNA在临床应用中的转化。
Functional Heterogeneity and Context-Dependent Roles of LncRNAs in Breast Cancer
肿瘤(癌症)患者之家