Yen Yun, Chu Tang-Yuan, Tseng Ruo-Chia
Center for Cancer Translational Research, Tzu Chi University, Hualien, Taiwan.
Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Tzu Chi Med J. 2025 Jun 30;37(3):235-246. doi: 10.4103/tcmj.tcmj_62_25. eCollection 2025 Jul-Sep.
This review focuses on the multifaceted roles of exosomal noncoding RNAs (ncRNAs) in colorectal cancer (CRC), utilizing the provided document as the primary source of information. Exosomes, nanoscale vesicles ranging from 30 to 150 nm, act as crucial mediators of intercellular communication, encapsulating bioactive molecules such as microRNAs (miRNAs) and long ncRNAs (lncRNAs). The biogenesis of exosomes involves the endocytic pathway, including the formation of multivesicular bodies and subsequent release of intraluminal vesicles into the extracellular space. This process is regulated by the endosomal sorting complex required for transport (ESCRT) machinery and other ESCRT-independent mechanisms, as well as RNA-binding proteins (RBPs) that selectively package ncRNAs. MiRNAs, shorter single-stranded RNA molecules, regulate gene expression post-transcriptionally by binding to target mRNAs, leading to translational repression or mRNA degradation. LncRNAs, longer RNA molecules, are involved in chromatin remodeling and transcriptional regulation and act as competing endogenous RNAs that modulate miRNA availability. Exosomal ncRNAs play a crucial role in tumorigenesis, where certain miRNAs promote proliferation while others act as tumor suppressors. Furthermore, these ncRNAs are central to the epithelial-mesenchymal transition, a critical process that facilitates metastasis. They also play a role in chemoresistance by modulating drug metabolism and apoptotic pathways. Exosomal ncRNAs also show promise as diagnostic and prognostic biomarkers due to their presence in body fluids and their association with disease progression. Moreover, they hold potential as therapeutic agents through RNA-based therapeutics and exosome-based drug delivery. The challenges involve standardizing exosome research, elucidating the underlying mechanisms, and ensuring successful clinical translation.
本综述以提供的文档为主要信息来源，重点关注外泌体非编码RNA（ncRNA）在结直肠癌（CRC）中的多方面作用。外泌体是直径为30至150纳米的纳米级囊泡，作为细胞间通讯的关键介质，包裹着生物活性分子，如微小RNA（miRNA）和长链非编码RNA（lncRNA）。外泌体的生物发生涉及内吞途径，包括多泡体的形成以及腔内囊泡随后释放到细胞外空间。这个过程由运输所需的内体分选复合物（ESCRT）机制和其他ESCRT非依赖机制以及选择性包裹ncRNA的RNA结合蛋白（RBP）调控。miRNA是较短的单链RNA分子，通过与靶mRNA结合在转录后调节基因表达，导致翻译抑制或mRNA降解。lncRNA是较长的RNA分子，参与染色质重塑和转录调控，并作为竞争性内源性RNA调节miRNA的可用性。外泌体ncRNA在肿瘤发生中起关键作用，某些miRNA促进增殖，而其他miRNA则作为肿瘤抑制因子。此外，这些ncRNA对于上皮-间质转化至关重要，上皮-间质转化是促进转移的关键过程。它们还通过调节药物代谢和凋亡途径在化疗耐药中发挥作用。外泌体ncRNA因其存在于体液中且与疾病进展相关，作为诊断和预后生物标志物也显示出前景。此外，它们通过基于RNA的疗法和基于外泌体的药物递送具有作为治疗剂的潜力。挑战包括使外泌体研究标准化、阐明潜在机制以及确保成功的临床转化。
