Identification of tRNA-derived small RNA (tsRNA) responsive to the tumor suppressor, RUNX1, in breast cancer.

Autor: Farina NH; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont.; Northern New England Clinical and Translational Research Network., Scalia S; Northern New England Clinical and Translational Research Network.; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, Vermont., Adams CE; Northern New England Clinical and Translational Research Network.; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, Vermont., Hong D; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont., Fritz AJ; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont., Messier TL; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont., Balatti V; Department of Cancer Biology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Veneziano D; Department of Cancer Biology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Lian JB; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont.; Northern New England Clinical and Translational Research Network., Croce CM; Department of Cancer Biology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Stein GS; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont.; Northern New England Clinical and Translational Research Network.; Department of Surgery, Larner College of Medicine, University of Vermont, Burlington, Vermont., Stein JL; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont.; Larner College of Medicine, University of Vermont Cancer Center, Burlington, Vermont.; Northern New England Clinical and Translational Research Network.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2020 Jun; Vol. 235 (6), pp. 5318-5327. Date of Electronic Publication: 2020 Jan 10.
DOI: 10.1002/jcp.29419
Abstrakt: Despite recent advances in targeted therapies, the molecular mechanisms driving breast cancer initiation, progression, and metastasis are minimally understood. Growing evidence indicate that transfer RNA (tRNA)-derived small RNAs (tsRNA) contribute to biological control and aberrations associated with cancer development and progression. The runt-related transcription factor 1 (RUNX1) transcription factor is a tumor suppressor in the mammary epithelium whereas RUNX1 downregulation is functionally associated with breast cancer initiation and progression. We identified four tsRNA (ts-19, ts-29, ts-46, and ts-112) that are selectively responsive to expression of the RUNX1 tumor suppressor. Our finding that ts-112 and RUNX1 anticorrelate in normal-like mammary epithelial and breast cancer lines is consistent with tumor-related activity of ts-112 and tumor suppressor activity of RUNX1. Inhibition of ts-112 in MCF10CA1a aggressive breast cancer cells significantly reduced proliferation. Ectopic expression of a ts-112 mimic in normal-like mammary epithelial MCF10A cells significantly increased proliferation. These findings support an oncogenic potential for ts-112. Moreover, RUNX1 may repress ts-112 to prevent overactive proliferation in breast epithelial cells to augment its established roles in maintaining the mammary epithelium.
(© 2020 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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