Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor-normal samples in lung adenocarcinoma
- 주제(키워드) biomarker , lung adenocarcinoma , miRNA , transcriptome analysis
- 주제(기타) Oncology
- 설명문(일반) [Yu, Namhee; Yong, Seunghui; Kim, Jaesang; Lee, Sanghyuk] Ewha Womans Univ, Dept Life Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Yu, Namhee; Jung, Yeonjoo; Seo, Jihae; Lee, Ye Eun; Kim, Jaesang; Lee, Sanghyuk] Ewha Womans Univ, ERCSB, Seoul, South Korea; [Kim, Hong Kwan; Kim, Jhingook] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Thorac & Cardiovasc Surg, Seoul 06351, South Korea; [Choi, Yoon-La] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol & Translat Genom, Seoul, South Korea; [Kim, Doyeon; Baek, Daehyun] Inst for Basic Sci Korea, Ctr RNA Res, Seoul, South Korea; [Baek, Daehyun] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea; [Lee, Jinseon] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Biomed Res Inst, Seoul, South Korea; [Lee, Seungjae; Lee, Jong Eun] DNA Link Inc, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 WILEY
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159706
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/1878-0261.12478
- PubMed https://pubmed.ncbi.nlm.nih.gov/30913346
초록/요약
The roles of miRNAs in lung cancer have not yet been explored systematically at the genome scale despite their important regulatory functions. Here, we report an integrative analysis of miRNA and mRNA sequencing data for matched tumor-normal samples from 109 Korean female patients with non-small-cell lung adenocarcinoma (LUAD). We produced miRNA sequencing (miRNA-Seq) and RNA-Seq data for 48 patients and RNA-Seq data for 61 additional patients. Subsequent differential expression analysis with stringent criteria yielded 44 miRNAs and 2322 genes. Integrative gene set analysis of the differentially expressed miRNAs and genes using miRNA-target information revealed several regulatory processes related to the cell cycle that were targeted by tumor suppressor miRNAs (TSmiR). We performed colony formation assays in A549 and NCI-H460 cell lines to test the tumor-suppressive activity of downregulated miRNAs in cancer and identified 7 novel TSmiRs (miR-144-5p, miR-218-1-3p, miR-223-3p, miR-27a-5p, miR-30a-3p, miR-30c-2-3p, miR-338-5p). Two miRNAs, miR-30a-3p and miR-30c-2-3p, showed differential survival characteristics in the Tumor Cancer Genome Atlas (TCGA) LUAD patient cohort indicating their prognostic value. Finally, we identified a network cluster of miRNAs and target genes that could be responsible for cell cycle regulation. Our study not only provides a dataset of miRNA as well as mRNA sequencing from the matched tumor-normal samples, but also reports several novel TSmiRs that could potentially be developed into prognostic biomarkers or therapeutic RNA drugs.
more