Direct circMAN1A2(2,3,4,5)-CENPB mRNA interaction regulates cell proliferation and cancer progression

Mei Cao, Guo-Hua Yuan, Shi-Meng Cao, Yu-Xin Liu, Chu-Xiao Liu, Yi-Feng Xu, Jia Wei, Yi-Lin Guo, Ling-Ling Chen and Li Yang ()
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Mei Cao: Fudan University
Guo-Hua Yuan: Chinese Academy of Sciences
Shi-Meng Cao: Chinese Academy of Sciences
Yu-Xin Liu: Chinese Academy of Sciences
Chu-Xiao Liu: Chinese Academy of Sciences
Yi-Feng Xu: Chinese Academy of Sciences
Jia Wei: Fudan University
Yi-Lin Guo: Fudan University
Ling-Ling Chen: Chinese Academy of Sciences
Li Yang: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Numerous covalently closed circular RNAs (circRNAs) are produced from back-splicing of eukaryotic exons, and multiple circRNAs can be generated from a single gene locus through alternative circularization (AC). However, functions of most AC circRNAs remain poorly understood. Here, we profile the landscape of AC across multiple cell lines and colorectal cancer (CRC) tissues, identifying predominantly expressed circRNAs (pe-circRNA) in each AC gene locus. Other than cell-type-specific expression of most top pe-circRNAs, circMAN1A2(2,3,4,5), a universally expressed pe-circRNA in examined samples, plays an important role in cell proliferation and CRC progression. Mechanistically, circMAN1A2(2,3,4,5) directly interacts with the 3′ untranslated region of Centromere Protein B (CENPB) mRNA via its characteristic back-splicing junction site, which enhances IGF2BP2-mediated CENPB mRNA stability. Inhibition of circMAN1A2(2,3,4,5) expression with locked nucleic acids represses CRC progression. These results uncover the prevalence of AC and the regulatory role of a specific AC circRNA, circMAN1A2(2,3,4,5), in cell proliferation and tumor progression.

Date: 2025
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DOI: 10.1038/s41467-025-63686-7

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