Abstract A31: Loss of RNA editing of miR-99a-5p is a potential prognostic biomarker in completely resected lung adenocarcinoma
Authors: Maemura Keita , Watanabe Kousuke , Ando Takahiro , Hiyama Noriko , Sakatani Toshio , Amano Yosuke , Kage Hidenori , Takai Daiya 
Published: February 2019

Abstract
Adenosine-to-Inosine (A-to-I) RNA editing of microRNAs affects tumor phenotypes in various cancer types both in vitro and in vivo. For example, in melanoma cell lines, reduced RNA editing in miR-455-5p promotes metastasis through inhibition of a tumor-suppressor gene, CPEB1. For another example, in glioblastoma cell lines, accumulation of unedited miR-376a-3p and downregulation of edited miR-376a-3p promotes migration and invasion through inhibition of RAP2A and upregulation of AMFR, respectively. However, the difference in the editing level of microRNAs between cancers and the corresponding noncancerous tissues in humans is largely unknown.
In this study, we examined microRNA deep sequencing data in silico. The previously reported perl scripts to detect microRNA editing events used release 18 (November 2011) from miRBase as reference. Therefore, we revised the scripts to use the latest version, release 21 (June 2014). Analysis of public data of 74 cases of lung adenocarcinoma from sequence read archive (SRA) revealed eight microRNAs that underwent A-to-I RNA editing in at least five cases of both the tumor samples and the corresponding noncancerous samples. The editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in the tumor samples than in the normal counterparts. The editing level of miR-200b-3p was higher in the tumor samples than in the normal counterparts. Among these four microRNAs, miR-99a-5p showed the largest difference in the editing level between the tumors and the normal counterparts.
Then we examined the editing level of miR-99a-5p in 50 cases of surgically resected lung adenocarcinoma at our institution by an original conventional sequence-based method. The editing level of miR-99a-5p was significantly lower in the tumor samples than the corresponding noncancerous samples in 19 cases (38%). The loss of RNA editing of miR-99a-5p was not associated with any clinical characteristics, such as sex, smoking history, pathologic stage, and EGFR mutation. These 19 cases showed a tendency toward a shorter recurrence-free survival (RFS) using the log rank test (P = 0.103) and a Cox proportional hazards model (hazard ratio, 1.91; 95% confidence interval, 0.87-4.19; P = 0.109). These results indicate that the loss of RNA editing of miR-99a-5p is a potential prognostic biomarker in patients with completely resected lung adenocarcinoma.
Citation Format: Keita Maemura, Kousuke Watanabe, Takahiro Ando, Noriko Hiyama, Toshio Sakatani, Yosuke Amano, Hidenori Kage, Daiya Takai. Loss of RNA editing of miR-99a-5p is a potential prognostic biomarker in completely resected lung adenocarcinoma [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A31.