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Background NUDT21 belongs to NUDT families, which is thought to play an essential role in cancer growth and progression in recent years. Abnormal NUDT21 expression is closely related to lung adenocarcinoma (LUAD). However, the expression level, gene regulation network, and prognostic value of NUDT21 in LUAD remain unclear. Besides, the active compounds of Pinellia ternata against LUAD are still not clear yet. Therefore, an in-depth study of the expression and gene regulation network of NUDT21 is of great theoretical significance and clinical demand for discovering new targets and strategies for the treatment of LUAD and the further improvement of the therapeutic effect of LUAD. Also, the targeted NUDT21 active ingredients of Pinellia ternata were sought to provide a theoretical basis for its clinical application in the treatment of LUAD. Methods A variety of online analysis tools were used in this study, including cBioPortal, ONCOMINE, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, Metascape, TIMER, TRRUST, The Human Protein Atlas, TCMSP, and AutoDock Vina. Results The levels of transcription and expression of NUDT21 were significantly increased in patients with LUAD. Gene altered of NUDT21 was up to 12% in LUAD patients. However, the promoter methylation level of NUDT21 in LUAD was lower compared to normal human. LUAD patients' survival with the low expression level of NUDT21 was better prognostic value than LUAD patients with high expression level. Forty-eight nodes and 572 edges were found in the PPI network constructed with NUDT21 and its neighboring genes. Regulatory region DNA binding, transcription regulatory region DNA binding, and regulatory region nucleic acid binding were the primary function of NUDT21 and its neighboring genes. The KEGG pathway of NUDT21 and its neighboring genes were mainly involved in the apelin signaling pathway, PI3K-Akt signaling pathway, and axon guidance. Our results showed that DNMT1, HDAC1, and MYC were the critical transcription factor targets involved in the network of NUDT21 and its neighboring genes. We also found that CDK1, ATM and PLK1 were main kinase targets in the NUDT21 kinase-target network. The NUDT21 miRNA-target network was associated with MIR-302C, MIR-9, and MIR-330. Moreover, the expression of NUDT21 was positively related to the infiltration of CD8 + T cells, macrophages, neutrophils and dendritic cell. 13 active compounds of Pinellia ternata were retrieved from the TCMSP. Among them, baicalein was the best combination with NUDT21. Conclusions Our results revealed the expression and potential regulatory network of NUDT21 in LUAD, laying a foundation for further research on the role of NUDT21 in cancer. Furthermore, we offer new therapeutic targets and prognostic biomarkers for the reference. Finally, we provide potential therapeutic drugs from traditional Chinese medicine in the treatment of LUAD. |
