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

Author

Listed:
  • Yvonne L. Chao

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill
    University of Pittsburgh
    University of Pittsburgh Medical Center Hillman Cancer Center)

  • Katherine I. Zhou

    (University of North Carolina Lineberger Comprehensive Cancer Center
    Duke University Medical Center
    University of North Carolina at Chapel Hill)

  • Kwame K. Forbes

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Alessandro Porrello

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill)

  • Gabrielle M. Gentile

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Yinzhou Zhu

    (Duke University Medical Center)

  • Aaron C. Chack

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Dixcy J. S. John Mary

    (University of Pittsburgh)

  • Haizhou Liu

    (University of Pittsburgh)

  • Eric Cockman

    (Duke University Medical Center)

  • Lincy Edatt

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill)

  • Grant A. Goda

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Justin J. Zhao

    (Duke University Medical Center)

  • Hala Abou Assi

    (Duke University Medical Center)

  • Hannah J. Wiedner

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Yihsuan Tsai

    (University of North Carolina Lineberger Comprehensive Cancer Center)

  • Lily Wilkinson

    (University of North Carolina Lineberger Comprehensive Cancer Center)

  • Amanda E. D. Swearingen

    (University of North Carolina Lineberger Comprehensive Cancer Center)

  • Lisa A. Carey

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill)

  • Jimena Giudice

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Daniel Dominguez

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Christopher L. Holley

    (Duke University Medical Center)

  • Chad V. Pecot

    (University of North Carolina Lineberger Comprehensive Cancer Center
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

Abstract

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.

Suggested Citation

  • Yvonne L. Chao & Katherine I. Zhou & Kwame K. Forbes & Alessandro Porrello & Gabrielle M. Gentile & Yinzhou Zhu & Aaron C. Chack & Dixcy J. S. John Mary & Haizhou Liu & Eric Cockman & Lincy Edatt & Gr, 2025. "Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59406-w
    DOI: 10.1038/s41467-025-59406-w
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