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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Biomarker of Pulmonary Inflammatory Response in LUAD: miR-584-5p Targets RAB23 to Suppress Inflammation Induced by LPS in A549 Cells

Author(s): Enyu Yang, Yinuo Hong, Cheng Xuan, Juan Xu, Qianyun Ding, Shuo Zhao, Haihan Ye, Xiaowei Fan, Zhenggang Jiang*, Siquan Zhang* and Xianfeng Ding*

Volume 30, Issue 10, 2023

Published on: 03 November, 2023

Page: [877 - 890] Pages: 14

DOI: 10.2174/0109298665248928231018070825

Price: $65

Abstract

Background: Pulmonary inflammatory response (PIR) is one of the prognostic risk factors of lung adenocarcinoma (LUAD), with a high mortality rate.

Objectives: This study aims to investigate prognostic microRNA (miRNA) to improve clinical prognosis prediction and postoperative inflammation treatment in LUAD patients.

Methods: About 201 differentially expressed microRNAs (DE-miRNAs) in LUAD were mined by differential analysis. Univariate/multivariate Cox analyses established and validated prognostic risk miRNAs in TCGA-LUAD. KEGG and GO were used to link risk signatures and biological functions. After 48 hours of exposure to 50 ng/mL LPS, the miR-584-5p/RAB23 regulatory network was verified in qRT-PCR, Western Blotting, and the Luciferase Reporter Assay in A549 cells.

Results: MiR-584-5p and miR-101-3p were validated as riskscore correlated with LUAD patients’ 1-year survival (p < 0.001) and participate in multiple inflammation-related pathways. RAB23, a RAS oncogene, is involved in inflammatory MAPK signaling. Evidence suggests that miR-584-5p regulates inflammation in LUAD by targeting RAB23. A549 cells were transfected with the mimic and inhibitor of miR-584-5p, confirming the negative regulatory relationship between miR-584-5p and RAB23. In the A549 induced by LPS, either over-expression of miR-584-5p or knock-down of RAB23 expression decreased the expression of inflammatory factors and increased cell viability.

Conclusion: Prognostic-related risk miR-584-5p can regulate the expression of RAB23 at both the mRNA and protein levels, thereby influencing the development of a PIR in LUAD. This will have significant implications for the clinical prognosis prediction and therapy decision-making of LUAD patients with PIR.

Keywords: Pulmonary inflammatory response, lung adenocarcinoma, miR-584-5p, prognosis, RAB23, riskscore, DE-miRNAs.

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