The Role of LINC01569/miR-4722-5p/RAB14 Regulatory Axis in Chronic Obstructive Pulmonary Disease-Related Inflammation...

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disorder. Its prevention and management have become increasingly challenging owing to subtle and easily overlooked early symptoms, warranting the exploration of detection markers. Hence, this study aimed to explore COPD-related competitive endogenous RNA (ceRNA) mechanisms with notable predictive value by leveraging bioinformatics methods. Herein, Gene Expression Omnibus, lncRNASNP2, and miRDB were used to construct a COPD-related ceRNA network, which was then assessed through Kyoto Encyclopedia of Gene and Genomes pathway analysis. The targeting relationship of identified axis was confirmed through RNA pull-down and dual-luciferase reporter assays. In total, 106 patients with stable COPD and 98 patients with acute exacerbation COPD (AECOPD) were enrolled. Binary logistic regression and receiver operating characteristic curve analyses were performed to evaluate the clinical significance of the identified axis. Additionally, its role in COPD-related inflammation was investigated in BEAS-2B cells treated with cigarette smoke extract (CSE). A potential ceRNA mechanism was identified involving LINC01569, miR-4722-5p, and RAB14, where LINC01569 overexpression promoted RAB14 expression by competitively binding to miR-4722-5p. Both LINC01569 and RAB14 were highly expressed in AECOPD, making them risk factors of COPD (odds ratio [OR] = 5.100 and 8.076, respectively), with their area under the curve (AUC) values for predicting disease progression being 0.878 and 0.822, respectively. In contrast, miR-4722-5p acted as a potential protective factor (OR = 0.448), with an AUC of 0.724 for predicting AECOPD occurrence. Their serum expression strongly correlated with inflammatory markers. In CSE-treated BEAS-2B cells, silencing LINC01569 upregulated miR-4722-5p, thereby suppressing RAB14 expression and reducing pro-inflammatory factor production. Altogether, the LINC01569/miR-4722-5p/RAB14 regulatory axis represents a potential ceRNA mechanism influencing COPD progression. It demonstrates significant predictive value for disease development and plays a crucial role in COPD-associated inflammatory processes.