Identification of novel interacts partners of ADAR1 enzyme mediating the oncogenic process in aggressive breast cancer

• Published in: Scientific reports Vol. 13; no. 1; pp. 8341 - 11
• Main Authors: Binothman, Najat, Aljadani, Majidah, Alghanem, Bandar, Refai, Mohammed Y., Rashid, Mamoon, Al Tuwaijri, Abeer, Alsubhi, Nouf H., Alrefaei, Ghadeer I., Khan, Muhammad Yasir, Sonbul, Sultan N., Aljoud, Fadwa, Alhayyani, Sultan, Abdulal, Rwaa H., Ganash, Magdah, Hashem, Anwar M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.05.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 631/67; Adenosine Deaminase - metabolism; Aggressive behavior; Breast; Breast cancer; Carcinoma; Clinical outcomes; Complement C4; Complement component C4; Gene expression; Histone H2A; Histones; Humanities and Social Sciences; Humans; Immunoprecipitation; Mass spectrometry; Mass spectroscopy; multidisciplinary; Proteins; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Triple Negative Breast Neoplasms - pathology; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-35517-6

Triple-negative breast cancer (TNBC) subtype is characterized by aggressive clinical behavior and poor prognosis patient outcomes. Here, we show that ADAR1 is more abundantly expressed in infiltrating breast cancer (BC) tumors than in benign tumors. Further, ADAR1 protein expression is higher in aggressive BC cells (MDA-MB-231). Moreover, we identify a novel interacting partners proteins list with ADAR1 in MDA-MB-231, using immunoprecipitation assay and mass spectrometry. Using iLoop, a protein–protein interaction prediction server based on structural features, five proteins with high iloop scores were discovered: Histone H2A.V, Kynureninase (KYNU), 40S ribosomal protein SA, Complement C4-A, and Nebulin (ranged between 0.6 and 0.8). In silico analysis showed that invasive ductal carcinomas had the highest level of KYNU gene expression than the other classifications (p < 0.0001). Moreover, KYNU mRNA expression was shown to be considerably higher in TNBC patients (p < 0.0001) and associated with poor patient outcomes with a high-risk value. Importantly, we found an interaction between ADAR1 and KYNU in the more aggressive BC cells. Altogether, these results propose a new ADAR-KYNU interaction as potential therapeutic targeted therapy in aggressive BC.