miR-335-5p Predicts Elevated Chronic Obstructive Pulmonary Disease (COPD) Susceptibility and Its Role in Human Bronchial Epithelial Cells Injury

miR-335-5p预测慢性阻塞性肺疾病(COPD)易感性升高及其在人类支气管上皮细胞损伤中的作用

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Abstract

PURPOSE: Chronic obstructive pulmonary disease (COPD) suffers from high prevalence, disability and mortality rates and a heavy economic burden. miR-335-5p takes part in multiple respiratory diseases such as pulmonary fibrosis, whereas its study in COPD has not been reported. The aim of our research was to explore miR-335-5p in predicting elevated COPD susceptibility and in human bronchial epithelial cells injury. PATIENTS AND METHODS: qRT-PCR was performed to examine miR-335-5p levels in serum and cells. ROC curve and logistic regression analyses were utilized to evaluate the predictive capacity of miR-335-5p for COPD susceptibility. Pearson correlation was used to assess the association of miR-335-5p with TNF-α, IL-6, FEV1, and FEV1/FVC. Human bronchial epithelial cells were exposed to cigarette smoke extract (CSE) conditions to simulate cell injury. Cell proliferation, apoptosis, inflammatory response and oxidative stress-related factors were assayed by CCK8, flow cytometry and ELISA, respectively. RESULTS: miR-335-5p is reduced on COPD patients. ROC curve recommended that miR-335-5p has high sensitivity (88.9%) and specificity (80.0%) to distinguish COPD from healthy individuals. Logistic regression showed that reduced miR-335-5p predicted elevated COPD susceptibility. Moreover, miR-335-5p was significantly negatively related to TNF-α and IL-6 and positively related to FEV1, and FEV1/FVC in COPD patients. Cellular experiments revealed that CSE treatment decreased miR-335-5p expression, repressed cell proliferation, facilitated apoptosis, raised TNF-α, IL-6, ROS, and MDA levels, and reduced SOD levels. miR-335-5p overexpression facilitated cell proliferation, suppressed apoptosis, diminished TNF-α, IL-6, ROS, and MDA levels, and elevated SOD levels, whereas knockdown of miR-335-5p reversed this trend. CONCLUSION: Downregulation of miR-335-5p increased COPD susceptibility and negatively correlated with inflammatory factors. Overexpression of miR-335-5p alleviated CSE-induced injury to human bronchial epithelial cells, which suggested that miR-335-5p may be a potential target for COPD treatment.

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