Bermúdez Mercedes, Martínez-Barajas Marcela Guadalupe, Bueno-Urquiza Lesly Jazmín, López-Gutiérrez Jorge Armando, Villegas-Mercado Carlos Esteban, López-Camarillo César
Faculty of Dentistry, Autonomous University of Chihuahua, Chihuahua 31000, Mexico.
University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico.
Cancers (Basel). 2024 Aug 10;16(16):2814. doi: 10.3390/cancers16162814.
microRNA-204-5p (miR-204) is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC, known as the hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, TGFBR2, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.
微小RNA-204-5p（miR-204）是一种小的非编码RNA，在乳腺癌（BC）的发生和发展中具有多种调节作用。miR-204与BC多步骤发展过程中获得的基本特征的形成有关，这些特征被称为癌症标志。它可能通过抑制血管生成、血管生成拟态、侵袭、迁移和转移等关键细胞过程，作为一种有效的肿瘤抑制因子发挥作用。它通过靶向参与这些过程的多个主控基因来实现这一点，这些基因包括缺氧诱导因子-1α（HIF-1α）、β-连环蛋白、血管内皮生长因子A（VEGFA）、转化生长因子β受体2（TGFBR2）、粘着斑激酶（FAK）、叉头框蛋白A1（FOXA1）等。此外，miR-204调节磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）等信号通路，并与HOTAIR和DSCAM-AS1长链非编码RNA相互作用，进一步影响肿瘤进展。除了对肿瘤细胞的直接作用外，miR-204还通过调节免疫细胞浸润、抑制促肿瘤细胞因子的产生以及潜在地影响免疫治疗反应来塑造肿瘤微环境。此外，miR-204在代谢重编程中起着关键作用，它直接抑制肿瘤细胞内的代谢基因，通过外泌体信号间接影响代谢，并重塑肿瘤微环境内的代谢通量。本综述旨在介绍关于miR-204在BC标志中的作用的当前知识的最新情况。总之，miR-204是BC中一个潜在的治疗靶点和预后标志物，强调需要进一步研究以充分阐明其在协调侵袭性BC行为中的复杂作用。
