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Circular RNA CLASP1 modulates the GLI1/SNAIL axis and enhances macrophage polarization in breast cancer




TekijätZhou, 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

KustantajaSpringer Science and Business Media LLC

Julkaisuvuosi2025

Lehti: Oncogene

Vuosikerta44

Aloitussivu4765

Lopetussivu4780

ISSN0950-9232

eISSN1476-5594

DOIhttps://doi.org/10.1038/s41388-025-03627-2

Julkaisun avoimuus kirjaamishetkelläEi avoimesti saatavilla

Julkaisukanavan avoimuus Osittain avoin julkaisukanava

Verkko-osoitehttps://doi.org/10.1038/s41388-025-03627-2

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/505443591


Tiivistelmä
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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Julkaisussa olevat rahoitustiedot
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).


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