Yilmaz Alper, Ari Yuka Selcen
Department of Molecular Biology and Genetics, Yildiz Technical University, Istanbul, 34220, Turkey.
Department of Genetics and Bioengineering, Alanya Alaaddin Keykubat University, Antalya, 07425, Turkey.
J Mol Med (Berl). 2025 Jan;103(1):33-49. doi: 10.1007/s00109-024-02503-y. Epub 2024 Dec 6.
The tumor microenvironment, which is the tailored physiological milieu of heterogeneous cancer cell populations surrounded by stromal and immune cells as well as extracellular matrix components, is a leading modulator of critical cancer hallmarks and one of the most significant prognostic indicators in breast cancer. In the last few decades, with the discovery of the interactions of ncRNAs with diverse cellular molecules, considerable emphasis has been devoted to understanding their direct and indirect roles in specific functions in breast cancer. Collectively, all of these have revealed that the competitive action of protein-coding RNAs and ncRNAs such as circRNAs and lncRNAs, which have a shared affinity for miRNAs, play a vital role in the molecular regulation of breast cancer. This phenomenon, termed as competing endogenous RNAs (ceRNAs), facilitates modeling the microenvironment through intercellular shuttles. Microenvironment ceRNA interactions have emerged as a frontier in the deep understanding of the complex mechanisms of breast cancer. In this review, we first discuss cellular ceRNAs in four key biological processes critical for microenvironmental regulation in breast cancer tissues: hypoxia, angiogenesis, immune regulations, and ECM remodeling. Further, we draw a complete portrait of microenvironment regulation by cell-to-cell cross-talk of shuttled ceRNAs and offer a framework of potential applications and challenges in overcoming the aggressive phenotype of the breast cancer microenvironment.
肿瘤微环境是由基质细胞、免疫细胞以及细胞外基质成分所包围的异质性癌细胞群体的特定生理环境，是关键癌症特征的主要调节因子，也是乳腺癌最重要的预后指标之一。在过去几十年中，随着非编码RNA（ncRNA）与多种细胞分子相互作用的发现，人们相当重视了解它们在乳腺癌特定功能中的直接和间接作用。总体而言，所有这些都表明，蛋白质编码RNA与circRNA和lncRNA等ncRNA的竞争作用，它们对微小RNA（miRNA）具有共同的亲和力，在乳腺癌的分子调控中起着至关重要的作用。这种现象被称为竞争性内源RNA（ceRNA），通过细胞间穿梭促进微环境建模。微环境ceRNA相互作用已成为深入理解乳腺癌复杂机制的前沿领域。在本综述中，我们首先讨论乳腺癌组织中对微环境调节至关重要的四个关键生物学过程中的细胞ceRNA：缺氧、血管生成、免疫调节和细胞外基质重塑。此外，我们通过穿梭ceRNA的细胞间相互作用描绘了微环境调节的完整图景，并提供了在克服乳腺癌微环境侵袭性表型方面潜在应用和挑战的框架。
