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

Cao M., Yuan G-H., Cao S-M., Liu Y-X., Liu C-X., Xu Y-F., Wei J., Guo Y-L., Chen L-L., Yang L.

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.

More information Original publication

DOI

10.1038/s41467-025-63686-7

Type

Journal article

Publication Date

2025-09-01T00:00:00+00:00

Volume

16

Addresses

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Keywords

Cell Line, Tumor, Humans, Colorectal Neoplasms, Disease Progression, RNA-Binding Proteins, Chromosomal Proteins, Non-Histone, RNA, Messenger, 3' Untranslated Regions, Cell Proliferation, Gene Expression Regulation, Neoplastic, RNA Stability, RNA, Circular