Open AccessEvaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer
Author(s) -
Che Pei Kung,
Kyle A. Cottrell,
Sua Ryu,
Emily R. Bramel,
Raleigh D. Kladney,
Emily A. Bao,
Eric C. Freeman,
Thwisha Sabloak,
Leonard B. Maggi,
Jason D. Weber
Publication year - 2020
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/s41388-020-01515-5
Subject(s) - triple negative breast cancer , gene knockdown , biology , breast cancer , cancer research , carcinogenesis , cancer , psychological repression , gene isoform , cell culture , gene expression , gene , genetics
Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer. Unlike other types of breast cancer that can be effectively treated by targeted therapies, no such targeted therapy exists for all TNBC patients. The ADAR1 enzyme carries out A-to-I editing of RNA to prevent sensing of endogenous double-stranded RNAs. ADAR1 is highly expressed in breast cancer including TNBC. Here, we demonstrate that expression of ADAR1, specifically its p150 isoform, is required for the survival of TNBC cell lines. In TNBC cells, knockdown of ADAR1 attenuates proliferation and tumorigenesis. Moreover, ADAR1 knockdown leads to robust translational repression. ADAR1-dependent TNBC cell lines also exhibit elevated IFN stimulated gene expression. IFNAR1 reduction significantly rescued the proliferative defects of ADAR1 loss. These findings establish ADAR1 as a novel therapeutic target for TNBC tumors.