circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.
Proceedings of the National Academy of Sciences of the United States of America(2023)
摘要
Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFβ-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFβ-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.
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关键词
Nedd4L,YBX1,circRNA,metastasis
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