Scholars@Duke

Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape.

Publication ,  Journal Article
Chao, YL; Zhou, KI; Forbes, KK; Porrello, A; Gentile, GM; Zhu, Y; Chack, AC; John Mary, DJS; Liu, H; Cockman, E; Edatt, L; Goda, GA; Zhao, JJ ...
Published in: Nat Commun
May 2, 2025
Published version (DOI) Link to item

Previously considered "housekeeping" genes, small nucleolar RNAs (snoRNAs) are increasingly understood to have wide-ranging functions in cancer, yet their role in metastasis has been less well studied. Here, we identify the snoRNA Snord67 as a regulator of lymph node (LN) metastasis in breast cancer. Snord67 expression is enriched in LN metastases in an immune-competent mouse model of female breast cancer. In an orthotopic breast cancer model, loss of Snord67 decreases LN metastasis. In a model of lymphatic metastasis, Snord67 loss decreases LN tumor growth and distant metastases. In breast cancer cell lines, Snord67 knockout results in loss of targeted 2'-O-methylation on U6 small nuclear RNA, as well as widespread changes in splicing. Together, these results demonstrate that Snord67 regulates splicing and promotes the growth of LN metastases and subsequent spread to distant metastases. SnoRNA-guided modifications of the spliceosome and regulation of splicing may represent a potentially targetable pathway in cancer.

Duke Scholars

Amanda Van Swearingen
Author Amanda Van Swearingen  
Katherine Zhou
Author Katherine Zhou  
Christopher Lee Holley
Author Christopher Lee Holley Medicine, Cardiology

Published In

Nat Commun

DOI

10.1038/s41467-025-59406-w

EISSN

2041-1723

Publication Date

May 2, 2025

Volume

16

Issue

1

Start / End Page

4118

Location

England

Related Subject Headings

  • Spliceosomes
  • RNA, Small Nucleolar
  • RNA, Small Nuclear
  • RNA Splicing
  • Neoplasm Metastasis
  • Mice
  • Lymphatic Metastasis
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chao, Y. L., Zhou, K. I., Forbes, K. K., Porrello, A., Gentile, G. M., Zhu, Y., … Pecot, C. V. (2025). Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape. Nat Commun, 16(1), 4118. https://doi.org/10.1038/s41467-025-59406-w
Chao, Yvonne L., Katherine I. Zhou, Kwame K. Forbes, Alessandro Porrello, Gabrielle M. Gentile, Yinzhou Zhu, Aaron C. Chack, et al. “Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape.” Nat Commun 16, no. 1 (May 2, 2025): 4118. https://doi.org/10.1038/s41467-025-59406-w.
Chao YL, Zhou KI, Forbes KK, Porrello A, Gentile GM, Zhu Y, et al. Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape. Nat Commun. 2025 May 2;16(1):4118.
Chao, Yvonne L., et al. “Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape.” Nat Commun, vol. 16, no. 1, May 2025, p. 4118. Pubmed, doi:10.1038/s41467-025-59406-w.
Chao YL, Zhou KI, Forbes KK, Porrello A, Gentile GM, Zhu Y, Chack AC, John Mary DJS, Liu H, Cockman E, Edatt L, Goda GA, Zhao JJ, Abou Assi H, Wiedner HJ, Tsai Y, Wilkinson L, Van Swearingen AED, Carey LA, Giudice J, Dominguez D, Holley CL, Pecot CV. Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape. Nat Commun. 2025 May 2;16(1):4118.

Published In

Nat Commun

DOI

10.1038/s41467-025-59406-w

EISSN

2041-1723

Publication Date

May 2, 2025

Volume

16

Issue

1

Start / End Page

4118

Location

England

Related Subject Headings

  • Spliceosomes
  • RNA, Small Nucleolar
  • RNA, Small Nuclear
  • RNA Splicing
  • Neoplasm Metastasis
  • Mice
  • Lymphatic Metastasis
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female