circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1

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...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2023-03, Vol.120 (13), p.e2215132120-e2215132120
Main Authors: Chen, Shuang, Li, Ke, Guo, Jiawei, Chen, Hai-Ning, Ming, Yue, Jin, Yang, Xu, Fuyan, Zhang, Tingting, Yang, Yang, Ye, Zixia, Liu, Wenrong, Ma, Hulin, Cheng, Jian, Zhou, Jian-Kang, Li, Zhang, Shen, Shu, Dai, Lunzhi, Zhou, Zong-Guang, Xu, Heng, Peng, Yong
Format: Article
Language:English
Subjects:
Biological Sciences
Biomarkers
Cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Humans
Metastases
Proteasomes
Proteins
RNA, Circular - genetics
RNA, Circular - metabolism
Tumors
Ubiquitin
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Y-Box-Binding Protein 1 - genetics
Y-Box-Binding Protein 1 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2215132120