Pamela R de Santiago1, Alejandro Blanco2, Fernanda Morales3, Katherine Marcelain4, Olivier Harismendy5, Marcela Sjöberg Herrera6, Ricardo Armisén7. 1. Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Center of Excellence in Precision Medicine, Pfizer Chile, Santiago, Chile. 2. Center of Excellence in Precision Medicine, Pfizer Chile, Santiago, Chile; Centro de Genética y Genómica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Chile. 3. Center of Excellence in Precision Medicine, Pfizer Chile, Santiago, Chile; Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 4. Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 5. Division of Biomedical Informatics, Department of Medicine, University of California San Diego, California, United States; Moores Cancer Center, University of California San Diego, California, United States. 6. Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: msjoberg@bio.puc.cl. 7. Centro de Genética y Genómica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Chile. Electronic address: rarmisen@udd.cl.
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 FINDINGS: 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-infiltrating 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. SIGNIFICANCE: 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.
AIMS: Breast cancer is one of the leading causes of womandeaths 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 FINDINGS: 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-infiltrating 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 cancerpatients. SIGNIFICANCE: 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.
Authors: Hongpan Zhang; Meihan Liu; Guobo Du; Bin Yu; Xiaojie Ma; Yan Gui; Lu Cao; Xianfu Li; Bangxian Tan Journal: J Cancer Res Clin Oncol Date: 2022-03-17 Impact factor: 4.553
Authors: Colin J Worby; Henry L Schreiber; Timothy J Straub; Lucas R van Dijk; Ryan A Bronson; Benjamin S Olson; Jerome S Pinkner; Chloe L P Obernuefemann; Vanessa L Muñoz; Alexandra E Paharik; Philippe N Azimzadeh; Bruce J Walker; Christopher A Desjardins; Wen-Chi Chou; Karla Bergeron; Sinéad B Chapman; Aleksandra Klim; Abigail L Manson; Thomas J Hannan; Thomas M Hooton; Andrew L Kau; H Henry Lai; Karen W Dodson; Scott J Hultgren; Ashlee M Earl Journal: Nat Microbiol Date: 2022-05-02 Impact factor: 30.964