RNA Editing Enzyme ADAR1 Suppresses the Mobility of Cancer Cells via ARPIN

Abstract

Deamination of adenine or cytosine in RNA, called RNA editing, is a constitutively active and common modification. The primary role of RNA editing is tagging RNA right after its synthesis so that the endogenous RNA is recognized as self and distinguished from exogenous RNA, such as viral RNA. In addition to this primary function, the direct or indirect effects on gene expression can be utilized in cancer where a high level of RNA editing activity persists. This report identified actin-related protein 2/3 complex inhibitor (ARPIN) as a target of ADAR1 in breast cancer cells. Our comparative RNA sequencing analysis in MCF7 cells revealed that the expression of ARPIN was decreased upon ADAR1 depletion with altered editing on its 3'UTR. However, the expression changes of ARPIN were not dependent on 3'UTR editing but relied on three microRNAs acting on ARPIN. As a result, we found that the migration and invasion of cancer cells were profoundly increased by ADAR1 depletion, and this cellular phenotype was reversed by the exogenous ARPIN expression. Altogether, our data suggest that ADAR1 suppresses breast cancer cell mobility via the upregulation of ARPIN.

Brief guide to RNA sequencing analysis for nonexperts in bioinformatics

“…Here, we briefly describe methods regarding how to perform transcriptome analyses and a mini-collection of publicly available transcriptome data. Although detailed protocols, workflows, parameters, and versions for each tool need to be modified depending on the aims of experiments ( Hao et al, 2023 , Hong and Jeong, 2023 , Jang et al, 2022 , Ju et al, 2023 , Park et al, 2023 ), our guideline will be valuable for biologists who are not bioinformaticians to analyze their own and publicly available RNA-seq data. Users will need to refer to other papers for assessing microarray, scRNA sequencing data ( Ryu et al, 2023 , Hwang, 2023 , Kim, 2023 , Kim and Lee, 2023 ), and hardware requirements for transcriptome analysis, which we did not include in this guideline.…”