Cotton Genomics and Genetics 2025, Vol.16, No.5, 232-240 http://cropscipublisher.com/index.php/cgg 232 Research Insight Open Access Circular RNAs as Molecular Sponges Modulating miRNA Activity in Cotton Kaiwen Liang Comprehensive Utilization Center, Hainan Institute of Tropical Agricultural Resouces, Sanya, 572025, Hainan, China Corresponding email: kaiwen.liang@hitar.org Cotton Genomics and Genetics, 2025, Vol.16, No.5 doi: 10.5376/cgg.2025.16.0023 Received: 22 Jul., 2025 Accepted: 31 Aug., 2025 Published: 20 Sep., 2025 Copyright © 2025 Liang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Liang K.W., 2025, Circular RNAs as molecular sponges modulating miRNA activity in cotton, Cotton Genomics and Genetics, 16(5): 232-240 (doi: 10.5376/cgg.2025.16.0023) Abstract Circular RNAs (circRNAs) are a unique class of noncoding RNAs with covalently closed loop structures that play a crucial role in gene regulation in eukaryotes. In cotton (Gossypium spp.), microRNAs (miRNAs) are central to posttranscriptional gene regulation, influencing growth, development, and stress responses. This study investigates the role of circRNAs as molecular sponges in regulating miRNA activity in cotton. We first describe the biogenesis of circRNAs, their structural classification, and key features such as stability and tissue-specific expression. We then examine in detail the mechanisms by which circRNAs sequester miRNAs, including a competing endogenous RNA (ceRNA) network framework and experimental approaches to validate their sponging activity. We then highlight the regulatory roles of circRNAs in cotton fiber development, stress adaptation, and defense signaling through the circRNA-miRNA-mRNA axis. This study also reviews the progress in circRNA discovery using high-throughput sequencing and computational methods, as well as the challenges faced in their annotation. A key case study illustrates how specific circular RNAs act as "sponges" for miR156 and miR828, regulating SPL transcription factors and influencing fiber phenotype. Finally, we explore the potential of circular RNAs as biotechnological tools and molecular targets in cotton breeding programs. This study highlights the potential of circular RNA research for improving cotton quality and stress tolerance while also identifying knowledge gaps and future directions for multi-omics integration and genome editing strategies. Keywords Circular RNA (circRNA); microRNA (miRNA) sponge; Cotton fiber development; Non-coding RNA regulation; Post-transcriptional gene regulation 1 Introduction Circular RNA (circRNA) has actually been present in cells for a long time, but it is only in recent years that the scientific community has come to understand it. At first, it was regarded as a "product of error" in the editing process and no one paid attention. However, as research deepened, it was found that it not only exists universally in eukaryotes such as plants, but also varies in expression among different tissues, cell types, and even at different developmental stages. These features make people start to re-examine its role. Its structure is quite unique-unlike other RNAs that have A 5' cap and a 3' poly (A) tail, it is a closed loop. This structure makes it more stable and less prone to degradation. Precisely because of this, it can persist in cells and perform functions, such as "adsorbing" miRNA, serving as a protein binding platform, or regulating the expression of certain genes (Huang et al., 2020; Miysir et al., 2022). When it comes to miRNA, it is another type of non-coding small RNA. Although it is short, it plays a key role in gene regulation. miRNA can bind to specific mrnas, rendering them dysfunctional or preventing them from being translated. Especially in cotton, miRNA has a significant impact-it is involved in both how the fibers grow and how the plants respond to external environmental stresses such as high temperatures and drought. If there are problems with miRNA regulation, the development and adaptability of cotton may be affected (Salih et al., 2021; Zhang et al., 2021). Interestingly, there is also "interaction" between circRNA and miRNA. Many circrnas can absorb mirnas like "sponges", preventing them from seeking their target genes. This "interference" mechanism may have played a role in some key processes of cotton, such as fiber development or stress response. In other words, circular RNA is not an obscure "accompaniment". It may be one of the driving forces behind the regulation of these important agronomic traits (Benchi et al., 2023).
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