Next Article in Journal
Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma
Previous Article in Journal
Engineered Artificial MicroRNA Precursors Facilitate Cloning and Gene Silencing in Arabidopsis and Rice
Previous Article in Special Issue
Potential of Transcript Editing Across Mitogenomes of Early Land Plants Shows Novel and Familiar Trends
Open AccessArticle

APOBEC3-Mediated RNA Editing in Breast Cancer is Associated with Heightened Immune Activity and Improved Survival

1
Department of Breast Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2
Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
3
Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA
4
Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
5
Department of Surgery, Yokohama City University, Yokohama 236-0004, Japan
6
Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5621; https://doi.org/10.3390/ijms20225621
Received: 20 October 2019 / Revised: 7 November 2019 / Accepted: 8 November 2019 / Published: 10 November 2019
(This article belongs to the Special Issue RNA Editing)
APOBEC3 enzymes contribute significantly to DNA mutagenesis in cancer. These enzymes are also capable of converting C bases at specific positions of RNAs to U. However, the prevalence and significance of this C-to-U RNA editing in any cancer is currently unknown. We developed a bioinformatics workflow to determine RNA editing levels at known APOBEC3-mediated RNA editing sites using exome and mRNA sequencing data of 1040 breast cancer tumors. Although reliable editing determinations were limited due to sequencing depth, editing was observed in both tumor and adjacent normal tissues. For 440 sites (411 genes), editing was determinable for ≥5 tumors, with editing occurring in 0.6%–100% of tumors (mean 20%, SD 14%) at an average level of 0.6%–20% (mean 7%, SD 4%). Compared to tumors with low RNA editing, editing-high tumors had enriched expression of immune-related gene sets, and higher T cell and M1 macrophage infiltration, B and T cell receptor diversity, and immune cytolytic activity. Concordant with this, patients with increased RNA editing in tumors had better disease- and progression-free survivals (hazard ratio = 1.67–1.75, p < 0.05). Our study identifies that APOBEC3-mediated RNA editing occurs in breast cancer tumors and is positively associated with elevated immune activity and improved survival. View Full-Text
Keywords: APOBEC; breast cancer; RNA editing; sequencing; tumor immune microenvironment APOBEC; breast cancer; RNA editing; sequencing; tumor immune microenvironment
Show Figures

Figure 1

MDPI and ACS Style

Asaoka, M.; Ishikawa, T.; Takabe, K.; Patnaik, S.K. APOBEC3-Mediated RNA Editing in Breast Cancer is Associated with Heightened Immune Activity and Improved Survival. Int. J. Mol. Sci. 2019, 20, 5621.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop