Life Sciences 268 (2021) 118956 Available online 29 December 2020 0024-3205/© 2021 Elsevier Inc. All rights reserved. Immune-related IncRNA LINC00944 responds to variations in ADAR1 levels and it is associated with breast cancer prognosis Pamela R. de Santiago a, b , Alejandro Blanco b, g , Fernanda Morales b, c , Katherine Marcelain c, d , Olivier Harismendy e, f , Marcela Sj¨ oberg Herrera a, * , Ricardo Armis´ en g, ** a Departamento de Biología Celular y Molecular, Facultad de Ciencias Biol´ ogicas, Pontifcia Universidad Cat´ olica de Chile, Santiago, Chile b Center of Excellence in Precision Medicine, Pfzer Chile, Santiago, Chile c Centro de Investigaci´ on y Tratamiento del C´ ancer, Facultad de Medicina, Universidad de Chile, Santiago, Chile d Departamento de Oncología B´ asico Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile e Division of Biomedical Informatics, Department of Medicine, University of California San Diego, California, United States f Moores Cancer Center, University of California San Diego, California, United States g Centro de Gen´ etica y Gen´ omica, Instituto de Ciencias e Innovaci´ on en Medicina, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Chile A R T I C L E INFO Keywords: Breast cancer Cancer lncRNAs LINC00944 ADAR1 Prognosis Tumor-infltrating lymphocytes Bioinformatics Guilt by association analysis ABSTRACT Aims: Breast cancer is one of the leading causes of woman deaths worldwide, being a major public health problem. It has been reported that the expression of the RNA-editing enzyme Adenosine Deaminase Acting on RNAs 1 (ADAR1) is upregulated in breast cancer, predicting poor prognosis in patients. A few reports in literature examine ADAR1 and long non-coding RNAs (lncRNAs) interplay in cancer and suggest key roles in cancer-related pathways. This study aimed to investigate whether ADAR1 could alter the expression levels of lncRNAs and explore how those changes are related to breast cancer biology. Main methods: ADAR1 overexpression and knockdown studies were performed in breast cancer cell lines to analyze the effects over lncRNAs expression. Guilt-by-Association correlation analysis of the TCGA-BRCA cohort was performed to predict the function of the lncRNA LINC00944. Key fndings: Here, we show that LINC00944 is responsive to ADAR1 up- and downregulation in breast cancer cells. We found that LINC00944 expression has a strong relationship with immune signaling pathways. Further assessment of the TCGA-BRCA cohort showed that LINC00944 expression was positively correlated to tumor- infltrating T lymphocytes and pro-apoptotic markers. Moreover, we found that LINC00944 expression was correlated to the age at diagnosis, tumor size, and estrogen and progesterone receptor expression. Finally, we show that low expression of LINC00944 is correlated to poor prognosis in breast cancer patients. Signifcance: Our study provides further evidence of the effect of ADAR1 over lncRNA expression levels, and on the participation of LINC00944 in breast cancer, suggesting to further investigate its potential role as prognostic biomarker. 1. Introduction Breast cancer is the most frequently diagnosed cancer and the lead- ing cause of cancer-related deaths in women [1]. The Global Cancer Observatory (GLOBOCAN) projected 2,088,849 cases in 2018, world- wide, which represented 11.6% of total cancer cases [1]. According to the American Cancer Society, in 2020, there will be diagnosed about 276,480 cases of invasive breast cancer and about 48,530 new cases of carcinoma in situ only in the United States, while about 42,170 women will die from breast cancer. These alarming numbers highlight the extent of this major public health problem and prove the need for broader knowledge in basic research, diagnosis, and treatment of breast cancer. The Adenosine Deaminase Acting on RNAs (ADAR) family of pro- teins is integrated by three members, ADAR1, ADAR2, and ADAR3, with * Correspondence to: M. Sj¨ oberg, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biol´ ogicas, Pontifcia Universidad Cat´ olica de Chile, Av. Libertador Bernardo O’Higgins 340, 8320000 Santiago, Chile. ** Correspondence to: R. Armis´ en, Centro de Gen´ etica y Gen´ omica, Instituto de Ciencias e Innovaci´ on en Medicina, Facultad de Medicina Clínica Alemana Uni- versidad del Desarrollo, Av. Las Condes 12461, 7590943 Santiago, Chile. E-mail addresses: msjoberg@bio.puc.cl (M. Sj¨ oberg Herrera), rarmisen@udd.cl (R. Armis´ en). Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie https://doi.org/10.1016/j.lfs.2020.118956 Received 16 July 2020; Received in revised form 4 December 2020; Accepted 16 December 2020