Dataset Information

M6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis.

ABSTRACT:

Background

Pulmonary fibrosis is difficult to treat. Early diagnosis and finding potential drug therapy targets of pulmonary fibrosis are particularly important. There were still various problems with existing pulmonary fibrosis markers, so it is particularly important to find new biomarkers and drug treatment targets. m6A (N6,2'-O-dimethyladenosine) RNA methylation was the cause of many diseases, and it is regulated by m6A methylation regulators. So, whether RNA methylation regulators can be a diagnostic marker and potential drug therapy target of early pulmonary fibrosis needs to be explored.

Materials and methods

Using GSE110147 and GSE33566 in the GEO database to predict the m6A methylation regulators that may be related to the development of pulmonary fibrosis, we used 10 mg/ml bleomycin to induce mouse pulmonary fibrosis models and human pulmonary fibrosis samples, to confirm whether this indicator can be an early diagnostic marker of pulmonary fibrosis.

Results

According to the database prediction results, METTL3 can predict the occurrence and development of pulmonary fibrosis, and the results of MASSON and HE staining show that the fibrosis model of mice is successful, and the fibrosis of human samples is obvious. The results of immunohistochemistry showed that the expression of METTL3 was significantly reduced in pulmonary fibrosis.

Conclusions

The m6A methylation regulator METTL3 can be considered as an important biomarker for diagnosing pulmonary fibrosis occurrence, furthermore it could be considered as a drug target because of its low expression in pulmonary fibrosis.

SUBMITTER: Deng MS

PROVIDER: S-EPMC9050297 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis.

Deng Meng-Sheng MS Chen Kui-Jun KJ Zhang Dong-Dong DD Li Guan-Hua GH Weng Chang-Mei CM Wang Jian-Min JM

Evidence-based complementary and alternative medicine : eCAM 20220421

<h4>Background</h4>Pulmonary fibrosis is difficult to treat. Early diagnosis and finding potential drug therapy targets of pulmonary fibrosis are particularly important. There were still various problems with existing pulmonary fibrosis markers, so it is particularly important to find new biomarkers and drug treatment targets. m6A (N6,2'-O-dimethyladenosine) RNA methylation was the cause of many diseases, and it is regulated by m6A methylation regulators. So, whether RNA methylation regulators c ...[more]

PMID: 35497924

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Project description:Molecular biology studies show that RNA N6-methyladenosine (m6A) modifications may take part in the incidence and development of idiopathic pulmonary fibrosis (IPF). Nonetheless, the roles of m6A regulators in IPF are not fully demonstrated. In this study, 12 significant m6A regulators were filtered out between healthy controls and IPF patients using GSE33566 dataset. Random forest algorithm was used to identify 11 candidate m6A regulators to predict the incidence of IPF. The 11 candidate m6A regulators included leucine-rich PPR motif-containing protein (LRPPRC), methyltransferase-like protein 3, FTO alpha-ketoglutarate dependent dioxygenase (FTO), methyltransferase-like 14/16, zinc finger CCCH domain-containing protein 13, protein virilizer homolog, Cbl proto-oncogene like 1, fragile X messenger ribonucleoprotein 1 and YTH domain containing 1/2. A nomogram model was constructed based on 11 candidate m6A regulators and considered beneficial to IPF patients using decision curve analysis. Consensus clustering method was used to distinctly divide IPF patients into two m6A patterns (clusterA and clusterB) based on 12 significant m6A regulators. M6A scores of all IPF patients were obtained using principal component analysis to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, patients in clusterB were correlated with Th17 and Treg cell infiltration, innate immunity and Th1 immunity, while those in clusterA were correlated with adaptive immunity and Th2 immunity. Patients in clusterB also had higher expressions of mesenchymal markers and regulatory factors of fibrosis but lower expressions of epithelial markers. Lastly and interestingly, two m6A regulators, LRPPRC (p = 0.011) and FTO (p = 0.042), were identified as novel prognostic genes in IPF patients for the first time using an external GSE93606 dataset. Both of them had a positive correlation with a better prognosis and may serve as therapy targets. Thus, we conducted virtual screening to discover potential drugs targeting LRPPRC and FTO in the treatment of IPF. In conclusion, m6A regulators are crucial to the onset, development and prognosis of IPF. Our study on m6A patterns may provide clues for clinical diagnosis, prognosis and targeted therapeutic drugs development for IPF.