KEY TAKEAWAYS
- The study aimed to unravel how snoRNAs regulate cancer stemness, crucial for understanding ribosome biosynthesis.
- U2AF2-SNORA68 enhanced TNBC stemness by sequestering RPL23 in the nucleolus and upregulating c-Myc, revealing new regulatory insights.
While small nucleolar RNAs (snoRNAs) play a crucial role in ribosome biosynthesis, their impact on cancer stemness in triple-negative breast cancer (TNBC) requires more investigation.
Wenrong Zhang and the team aimed to investigate the role of snoRNAs in regulating cancer stemness in ribosome biosynthesis.
The study assessed SNORA68 expression in breast cancer tissues via in situ hybridization and qRT-PCR. Proliferation, migration, apoptosis, and stemness analyses were employed to ascertain SNORA68’s role in carcinogenesis and stemness preservation. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation, and co-immunoprecipitation assays were conducted.
SNORA68 displayed elevated expression levels in TNBC, significantly correlating with tumor size (P= 0.048), ki-67 level (P= 0.037), and TNM stage (P= 0.015). Patients achieving clinical benefit exhibited lower plasma SNORA68 concentration. SNORA68-high patients experienced notably shorter disease-free survival (DFS) (P= 0.036).
Functionally, SNORA68 enhanced TNBC cell stemness and carcinogenesis in vitro and in vivo. Moreover, increased SNORA68 expression resulted in elevated nucleolar RPL23 expression, with U2AF2 binding facilitating RPL23 retention in the nucleolus. Subsequently, nucleolar RPL23 upregulated c-Myc expression. This pathway’s validation was accomplished using a xenograft model.
The study concluded that U2AF2-SNORA68 enhances TNBC stemness by retaining RPL23 in the nucleolus and elevating c-Myc expression, offering novel insights into stemness regulatory mechanisms.
Research was funded by the National Natural Science Foundation of China and the Beijing Health Promotion Association—Young Breast Surgeon Research Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38594783/
Zhang W, Song X, Jin Z, et al. (2024) “U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression.” Breast Cancer Res. 2024 Apr 9;26(1):60. doi: 10.1186/s13058-024-01817-6. PMID: 38594783; PMCID: PMC11005140.
