Systematic identification of clinically relevant miRNAs for potential miRNA-based therapy in lung adenocarcinoma.

Abstract

Lung adenocarcinoma (LUAD), the most common histological type of non-small cell lung cancer, is one of the most malignant and deadly diseases. Current treatments for advanced LUAD patients are far from ideal and require further improvements. Here, we utilized a systematic integrative analysis of LUAD microRNA sequencing (miRNA-seq) and RNA-seq data from The Cancer Genome Atlas (TCGA) to identify clinically relevant tumor suppressor miRNAs. Three miRNA candidates (miR-195-5p, miR-101-3p, and miR-338-5p) were identified based on their differential expressions, survival significance levels, correlations with targets, and an additive effect on survival among them. We further evaluated mimics of the three miRNAs to determine their therapeutic potential in inhibiting cancer progression. The results showed not only that each of the miRNA mimics alone but also the three miRNA mimics in combination were efficient at inhibiting tumor growth and progression with equal final concentrations, meaning that the three miRNA mimics in combination were more effective than the single miRNA mimics. Moreover, the combined miRNA mimics provided significant therapeutic effects in terms of reduced tumor volume and metastasis nodules in lung tumor animal models. Hence, our findings show the potential of using the three miRNAs in combination to treat LUAD patients with poor survival outcomes.

• Authors: Shu-Hsuan Liu, Kai-Wen Hsu, Yo-Liang Lai, Yu-Feng Lin, Fang-Hsin Chen, Pei-Hwa Peng, Li-Jie Lin, Heng-Hsiung Wu, Chia-Yang Li, Shu-Chi Wang, Min-Zu Wu, Yuh-Pyng Sher, Wei-Chung Cheng
• Journal: Molecular therapy. Nucleic acids (Mol Ther Nucleic Acids) Vol. 25 Pg. 1-10 (Sep 03 2021) ISSN: 2162-2531 [Print] United States
• PMID: 34141460 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors.