A preliminary study on the screening and mechanism of miRNA as a biomarker for patients with different progressive chronic obstructive pulmonary disease (COPD)
Siming Tao, Chunyan Liao, Yide Wang, Dan Xu, Zheng Li, Fengsen Li- Organic Chemistry
- Computer Science Applications
- Drug Discovery
- General Medicine
aims:
This study aimed to explore the specific differential markers between the two extreme phenotypes of "fast" and "slow" progression of COPD and provide a theoretical basis for the treatment and prognosis evaluation of COPD from the perspective of its progression speed.
background:
Chronic obstructive pulmonary disease (COPD) is a smoking- and age-related disease, which is mainly characterized by persistent respiratory symptoms and restricted airflow. When COPD occurs, the lung function of patients cannot be completely reversed and progressed. However, the progressive development of lung function in the different types of patients is significantly different. The specific clinical diagnosis and treatment showed two types of phenotypes with significant differences, including "fast" disease progression, having a short course of the disease, but rapid deterioration of pulmonary function level and systemic respiratory symptoms, and "slow" disease progression, having a long disease course, but relatively stable pulmonary function level and systemic respiratory symptoms.
objective:
In this study, a high-throughput sequencing technology was used to screen the differentially expressed miRNA in the patients with "fast" and "slow" progression of chronic obstructive pulmonary disease (COPD). Moreover, the possible mechanism, affecting the progression of COPD, was preliminarily analyzed based on the target genes of candidate miRNAs.
method:
"fast" included 6 cases, "slow" and Normal included 5 cases, and COPD included 3 cases. The peripheral blood samples were taken from the participants, followed by total RNA extraction and high throughput miRNA sequencing. The differentially expressed miRNAs among the different progressive COPD groups were identified using bioinformatics analysis. Then, the candidate miRNAs were externally verified. In addition, the target gene of this miRNA was identified and its effects on the cell activity, cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed.
result:
As compared to the Normal group, a total of 35, 16, and 7 differentially expressed miRNAs were identified in the "fast" progressive COPD, "slow" progressive COPD, and COPD group, respectively. The results were further confirmed using dual-luciferase reporter assay and transfection tests with phosphoinositide- 3-kinase, regulatory subunit 2 (PIK3R2) as a target gene of miR-4433a-5p; the result showed a negative regulatory correlation between the miRNA and its target gene. The phenotype detection showed that the activation of the phosphatidylinositol 3 kinase(PI3K) /protein kinase B(AKT) signaling pathway might participate in the progression of COPD by promoting the proliferation of inflammatory A549 cells and inhibiting cellular apoptosis.
conclusion:
MiR-4433a-5p can be used as a marker and potential therapeutic target for the progression of COPD. As a target gene of miR-4433a-5p, PIK3R2 can affect the progression of COPD by regulating phenotypes, such as cellular proliferation and apoptosis.
other:
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