Owida Hamza Abu, Saleh Raed Obaid, Mohammad Suleiman Ibrahim, Vasudevan Asokan, Roopashree R, Kashyap Aditya, Nanda Anima, Ray Subhashree, Hussein Ahmed, Yasin Hatif Abdulrazaq
Department of Medical Engineering, Faculty of Engineering, Al-Ahliyya Amman University, Amman, Jordan.
Department of Medical Laboratories Techniques, College of Health and Medical Techniques, University of Al Maarif, Al Anbar, 31001, Iraq.
Med Oncol. 2025 May 2;42(6):191. doi: 10.1007/s12032-025-02727-z.
Hypoxia, characterized by reduced oxygen levels, plays a pivotal role in cancer progression, profoundly influencing tumor behavior and therapeutic responses. A hallmark of solid tumors, hypoxia drives significant metabolic adaptations in cancer cells, primarily mediated by hypoxia-inducible factor-1α (HIF-1α), a key transcription factor activated in low-oxygen conditions. This hypoxic environment promotes epithelial-mesenchymal transition (EMT), enhancing cancer cell migration, metastasis, and the development of cancer stem cell-like properties, which contribute to therapy resistance. Moreover, hypoxia modulates the expression of circular RNAs (circRNAs), leading to their accumulation in the tumor microenvironment. These hypoxia-responsive circRNAs regulate gene expression and cellular processes critical for cancer progression, making them promising candidates for diagnostic and prognostic biomarkers in various cancers. This review delves into the intricate interplay between hypoxic circRNAs, microRNAs, and RNA-binding proteins, emphasizing their role as molecular sponges that modulate gene expression and signaling pathways involved in cell proliferation, apoptosis, and metastasis. It also explores the relationship between circRNAs and the tumor microenvironment, particularly how hypoxia influences their expression and functional dynamics. Additionally, the review highlights the potential of circRNAs as diagnostic and prognostic tools, as well as their therapeutic applications in innovative cancer treatments. By consolidating current knowledge, this review underscores the critical role of circRNAs in cancer biology and paves the way for future research aimed at harnessing their unique properties for clinical advancements. Specifically, this review examines the biogenesis, expression patterns, and mechanistic actions of hypoxic circRNAs, focusing on their ability to act as molecular sponges for microRNAs and their interactions with RNA-binding proteins. These interactions impact key signaling pathways related to tumor growth, metastasis, and drug resistance, offering new insights into the complex regulatory networks governed by circRNAs under hypoxic stress.
缺氧以氧水平降低为特征，在癌症进展中起关键作用，深刻影响肿瘤行为和治疗反应。作为实体瘤的一个标志，缺氧驱动癌细胞发生显著的代谢适应，主要由缺氧诱导因子-1α（HIF-1α）介导，HIF-1α是在低氧条件下被激活的关键转录因子。这种缺氧环境促进上皮-间质转化（EMT），增强癌细胞迁移、转移以及癌症干细胞样特性的发展，这些特性导致治疗耐药性。此外，缺氧调节环状RNA（circRNA）的表达，导致它们在肿瘤微环境中积累。这些缺氧反应性circRNA调节对癌症进展至关重要的基因表达和细胞过程，使其成为各种癌症诊断和预后生物标志物的有希望的候选者。本综述深入探讨缺氧circRNA、微小RNA和RNA结合蛋白之间的复杂相互作用，强调它们作为分子海绵调节参与细胞增殖、凋亡和转移的基因表达和信号通路的作用。它还探讨了circRNA与肿瘤微环境之间的关系，特别是缺氧如何影响它们的表达和功能动态。此外，该综述强调了circRNA作为诊断和预后工具的潜力，以及它们在创新癌症治疗中的治疗应用。通过整合当前知识，本综述强调了circRNA在癌症生物学中的关键作用，并为未来旨在利用其独特特性实现临床进展的研究铺平了道路。具体而言，本综述研究了缺氧circRNA的生物发生、表达模式和作用机制，重点关注它们作为微小RNA分子海绵的能力以及它们与RNA结合蛋白的相互作用。这些相互作用影响与肿瘤生长、转移和耐药性相关的关键信号通路，为缺氧应激下由circRNA控制的复杂调控网络提供了新的见解。
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