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Breast Cancer Research
Published in: Breast Cancer Research 1/2024

Open Access 01-12-2024 | Breast Cancer | Research

U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression

Authors: Wenrong Zhang, Xinyue Song, Zining Jin, Yiqi Zhang, Shan Li, Feng Jin, Ang Zheng

Published in: Breast Cancer Research | Issue 1/2024

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Abstract

Background

Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated.

Methods

SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted.

Results

SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model.

Conclusion

U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.
Appendix
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Metadata
Title
U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression
Authors
Wenrong Zhang
Xinyue Song
Zining Jin
Yiqi Zhang
Shan Li
Feng Jin
Ang Zheng
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2024
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-024-01817-6

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