Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma
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‐cel...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-06-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12478 |
| _version_ | 1819157474518761472 |
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| author | Namhee Yu Seunghui Yong Hong Kwan Kim Yoon‐La Choi Yeonjoo Jung Doyeon Kim Jihae Seo Ye Eun Lee Daehyun Baek Jinseon Lee Seungjae Lee Jong Eun Lee Jaesang Kim Jhingook Kim Sanghyuk Lee |
| author_facet | Namhee Yu Seunghui Yong Hong Kwan Kim Yoon‐La Choi Yeonjoo Jung Doyeon Kim Jihae Seo Ye Eun Lee Daehyun Baek Jinseon Lee Seungjae Lee Jong Eun Lee Jaesang Kim Jhingook Kim Sanghyuk Lee |
| author_sort | Namhee Yu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T16:09:20Z |
| format | Article |
| id | doaj.art-6f5e09f0814c4d4d8f6775ca1d281234 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-22T16:09:20Z |
| publishDate | 2019-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-6f5e09f0814c4d4d8f6775ca1d2812342022-12-21T18:20:31ZengWileyMolecular Oncology1574-78911878-02612019-06-011361356136810.1002/1878-0261.12478Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinomaNamhee Yu0Seunghui Yong1Hong Kwan Kim2Yoon‐La Choi3Yeonjoo Jung4Doyeon Kim5Jihae Seo6Ye Eun Lee7Daehyun Baek8Jinseon Lee9Seungjae Lee10Jong Eun Lee11Jaesang Kim12Jhingook Kim13Sanghyuk Lee14Department of Life Science Ewha Womans University Seoul KoreaDepartment of Life Science Ewha Womans University Seoul KoreaDepartment of Thoracic and Cardiovascular Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul KoreaDepartment of Pathology and Translational Genomics Samsung Medical Center Sungkyunkwan University School of Medicine Seoul KoreaEwha Research Center for Systems Biology (ERCSB) Ewha Womans University Seoul KoreaCenter for RNA Research Institute for Basic Science Seoul KoreaEwha Research Center for Systems Biology (ERCSB) Ewha Womans University Seoul KoreaEwha Research Center for Systems Biology (ERCSB) Ewha Womans University Seoul KoreaCenter for RNA Research Institute for Basic Science Seoul KoreaSamsung Biomedical Research Institute Samsung Medical Center Sungkyunkwan University School of Medicine Seoul KoreaDNA Link Inc. Seoul KoreaDNA Link Inc. Seoul KoreaDepartment of Life Science Ewha Womans University Seoul KoreaDepartment of Thoracic and Cardiovascular Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul KoreaDepartment of Life Science Ewha Womans University Seoul KoreaThe 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.https://doi.org/10.1002/1878-0261.12478biomarkerlung adenocarcinomamiRNAtranscriptome analysis |
| spellingShingle | Namhee Yu Seunghui Yong Hong Kwan Kim Yoon‐La Choi Yeonjoo Jung Doyeon Kim Jihae Seo Ye Eun Lee Daehyun Baek Jinseon Lee Seungjae Lee Jong Eun Lee Jaesang Kim Jhingook Kim Sanghyuk Lee Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma Molecular Oncology biomarker lung adenocarcinoma miRNA transcriptome analysis |
| title | Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma |
| title_full | Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma |
| title_fullStr | Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma |
| title_full_unstemmed | Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma |
| title_short | Identification of tumor suppressor miRNAs by integrative miRNA and mRNA sequencing of matched tumor–normal samples in lung adenocarcinoma |
| title_sort | identification of tumor suppressor mirnas by integrative mirna and mrna sequencing of matched tumor normal samples in lung adenocarcinoma |
| topic | biomarker lung adenocarcinoma miRNA transcriptome analysis |
| url | https://doi.org/10.1002/1878-0261.12478 |
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