A1 Refereed original research article in a scientific journal
Circular RNA CLASP1 modulates the GLI1/SNAIL axis and enhances macrophage polarization in breast cancer
Authors: Zhou, Lijun; Liu, Mei; Liu, Fujun; Wang, Zhengkun; Li, Xinyu; Peng, Xiaoyu; Ma, Wenqiang; Guo, Peilan; Yuan, Lifang; Wolczynski, Slawomir; Rahman, Nafis Ahmed; Song, Wei; Li, Xiangdong
Publisher: Springer Science and Business Media LLC
Publication year: 2025
Journal: Oncogene
Volume: 44
First page : 4765
Last page: 4780
ISSN: 0950-9232
eISSN: 1476-5594
DOI: https://doi.org/10.1038/s41388-025-03627-2
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1038/s41388-025-03627-2
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/505443591
Breast cancer (BC) is the most prevalent malignancy among women worldwide. Growing evidence highlights the crucial role of circular RNAs (circRNAs) in BC carcinogenesis; however, their underlying mechanisms remain largely unknown. In this study, we identify circCLASP1, which is significantly upregulated in BC tissues (n = 65) and serum samples (n = 61). Its expression correlates with lymph node metastasis, ki67 expression, and tumor size. Receiver operation characteristic (ROC) curve analysis reveals area under the curve (AUC) values of 0.8196 (BC tissues) and 0.8902 (BC serum), respectively. Functionally, circCLASP1 knockdown significantly suppresses BC cell proliferation, migration, and invasion. Mechanistically, circCLASP1 prevents the ubiquitin-mediated degradation of GLI1 protein by facilitating its interaction with CCT2, thereby stabilizing GLI1. Moreover, circCLASP1 enhances the nuclear accumulation of GLI1, leading to increased SNAIL expression and thereby upregulating the expression of CCL2 and CCL5, which in turn promotes macrophage M2 polarization, ultimately resulting in BC progression and subsequent lung metastasis. Further analysis reveals that U2AF2 regulates circCLASP1 biogenesis. Collectively, these findings demonstrate that circCLASP1 promotes BC progression and an immunosuppressive microenvironment via the CCT2/GLI1/SNAIL axis, highlighting its potential as a prognostic biomarker and therapeutic target for BC.
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Funding information in the publication:
This study was supported by grants from National Natural Science Foundation of China (82171854), the 2115 Talent Development Program of China Agricultural University, and Medical University of Bialystok, Poland (B.SUB.25.379).
