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Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma
Keita Maemura1, Kousuke Watanabe1, Takahiro Ando1
1Department of Respiratory Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Abstract:
Adenosine-to-inosine (A-to-I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have shown several microRNAs that undergo A-to-I editing in human cancers, some of which have been reported to be associated with prognosis. Herein, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico in order to identify A-to-I microRNA editing events. Editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in AD than in NC and, in a large number of cases, the editing level of miR-200b-3p was higher in AD than in NC. Difference in the editing level between AD and NC was largest for miR-99a-5p. Then, we examined the editing level of miR-99a-5p in 50 surgically resected lung adenocarcinoma cases at our institution by a conventional sequence-based method, and its association with clinical outcomes. The editing level of miR-99a-5p was significantly lower in 19 cases of AD (38%) than in corresponding NC. These cases showed a shorter overall survival as assessed using the log-rank test (P = .047). This trend was consistent with previous analyses of TCGA dataset. The altered editing level of microRNAs in lung adenocarcinoma could serve as a potential biomarker.
Insights
Adenosine-to-inosine microRNA editing, particularly in miR-99a-5p, is altered in lung adenocarcinoma. Lower editing levels of this microRNA correlate with shorter patient survival, suggesting its potential as a biomarker.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Adenosine-to-inosine (A-to-I) microRNA editing is implicated in cancer development and progression.
- Previous studies using The Cancer Genome Atlas (TCGA) dataset identified A-to-I edited microRNAs associated with cancer prognosis.
Purpose of the Study:
- To investigate A-to-I microRNA editing events in lung adenocarcinoma (AD) by analyzing small RNA deep sequencing data.
- To assess the association between the editing level of specific microRNAs, particularly miR-99a-5p, and clinical outcomes in lung adenocarcinoma patients.
Main Methods:
- In silico analysis of published small RNA deep sequencing data from 74 lung adenocarcinoma (AD) and normal counterpart (NC) specimens.
- Conventional sequence-based analysis of miR-99a-5p editing levels in 50 surgically resected lung adenocarcinoma cases.
- Statistical analysis, including log-rank test, to evaluate the association with overall survival.
Main Results:
- Editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in AD compared to NC.
- Editing level of miR-200b-3p was higher in AD than in NC in a significant number of cases.
- The most substantial difference in editing level between AD and NC was observed for miR-99a-5p.
- Lower miR-99a-5p editing levels in AD specimens (38% of cases) were significantly associated with shorter overall survival (P = 0.047).
Conclusions:
- Altered A-to-I microRNA editing, specifically decreased miR-99a-5p editing, is a feature of lung adenocarcinoma.
- The editing level of miR-99a-5p may serve as a potential prognostic biomarker for lung adenocarcinoma.
- These findings align with previous TCGA dataset analyses, reinforcing the clinical relevance of microRNA editing in cancer.
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