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Differential miRNA Profiling Reveals miR-4433a-5p as a Key Regulator of Chronic Obstructive Pulmonary Disease Progression via PIK3R2- mediated Phenotypic Modulation.
Tao, Siming; Liao, Chunyan; Wang, Yide; Xu, Dan; Li, Zheng; Li, Fengsen.
Afiliación
  • Tao S; Department of Respiratory and Critical Care Medicine, Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • Liao C; Department of Respiratory and Critical Care Medicine, Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • Wang Y; Department of Respiratory and Critical Care Medicine, Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • Xu D; Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
  • Li Z; Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
  • Li F; Department of Respiratory and Critical Care Medicine, Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Comb Chem High Throughput Screen ; 27(16): 2323-2334, 2024.
Article en En | MEDLINE | ID: mdl-38178680
ABSTRACT

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.

METHODS:

The "fast" progressive COPD group included 6 cases, "slow" and Normal progressive COPD groups included 5 cases each, and COPD group 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 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 cell activity, cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed.

RESULTS:

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 group, 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.

CONCLUSIONS:

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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Progresión de la Enfermedad / Fosfatidilinositol 3-Quinasas / Enfermedad Pulmonar Obstructiva Crónica / MicroARNs Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Comb Chem High Throughput Screen / Combinatorial chemistry & high throughput screening (Online) Asunto de la revista: BIOLOGIA MOLECULAR / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Progresión de la Enfermedad / Fosfatidilinositol 3-Quinasas / Enfermedad Pulmonar Obstructiva Crónica / MicroARNs Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Comb Chem High Throughput Screen / Combinatorial chemistry & high throughput screening (Online) Asunto de la revista: BIOLOGIA MOLECULAR / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China