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Identification of tRNA‐derived small RNA (tsRNA) responsive to the tumor suppressor, RUNX1, in breast cancer
Author(s) -
Fariicholas H.,
Scalia Stephanie,
Adams Caroline E.,
Hong Deli,
Fritz Andrew J.,
Messier Terri L.,
Balatti Veronica,
Veneziano Dario,
Lian Jane B.,
Croce Carlo M.,
Stein Gary S.,
Stein Janet L.
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29419
Subject(s) - ectopic expression , cancer research , runx1 , suppressor , breast cancer , biology , tumor progression , cancer , transcription factor , metastasis , mammary tumor , downregulation and upregulation , cell culture , gene , genetics
Abstract 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.