Identification of m6A-modified gene signatures in lung adenocarcinoma tumorigenesis and their potential role in drug resistance
Abstract Background Lung cancer is one of the most commonly diagnosed cancers. N 6-methyladenosine (m6A) modification has a profound impact on RNA translation, splicing, transportation, and stability. Aims This research aimed to identify and verify m6A-modified signatures for Lung adenocarcinoma (LU...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-03-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-02106-0 |
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| Summary: | Abstract Background Lung cancer is one of the most commonly diagnosed cancers. N 6-methyladenosine (m6A) modification has a profound impact on RNA translation, splicing, transportation, and stability. Aims This research aimed to identify and verify m6A-modified signatures for Lung adenocarcinoma (LUAD) tumorigenesis. Objective Our previous mRNA-seq and m6A-seq data from 26 pairs of LUAD samples and tumor-adjacent normal tissues are used. Methods Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) analysis were used to estimate the significance of 37 collected m6A regulators. WGCNA was constructed to identify the genes correlated with LUAD tumorigenesis. Pearson correlation analysis between mRNA-seq and m6A-seq data was used to identify the m6A-correlation genes. Results LASSO-Cox analysis identified 18 m6A significant regulators. The top 3 regulators, including METTL16, FTO, and SRSF10, and their downstream genes which were reported in the literature were analysed to confirm their role in LUAD tumorigenesis. Blue and brown coexpression modules were chosen as key modules for LUAD tumorigenesis. At last, we intersected Lasso-downstream genes, m6A-correlation genes, with blue or brown module genes. As a result, 56 m6A-modified gene signatures were obtained. Among them, AKAP9, PLXNB2, BRPF3, HPS4, EXOC7, and KLF6 have an inconsistent expression in protein and mRNA levels, probably due to m6A modification. In addition, these genes may be involved in regulating drug resistance. Conclusions 56 m6A-modified gene signatures for LUAD tumorigenesis were obtained from Pearson correlation analysis between mRNA-seq and m6A-seq data, along with LASSO and WGCNA analysis. Among them, AKAP9, PLXNB2, BRPF3, HPS4, EXOC7 and KLF6 play a crucial role in LUAD tumorigenesis in an m6A modification-dependent manner. |
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| ISSN: | 2730-6011 |