<p>Nasal polyps (NPs) are benign, inflammatory soft tissue growths in the nasal and paranasal sinus passages that are closely associated with chronic rhinosinusitis (CRS), which has a major influence on patients’ quality of life. This study aimed to investigate the role of miR-155-5p, its target genes, and oxidative stress in the molecular mechanisms driving NP formation. A total of 133 patients, including those with NPs (<i>n</i> = 65) and middle concha bullosa (<i>n</i> = 68), were evaluated via endoscopic examination and computed tomography. Tissue samples were stained with hematoxylin and eosin to examine structural alterations, and TUNEL labeling was used to detect apoptotic cells. Quantitative RT-qPCR was utilized to quantify miR-155-5p and its target genes (PI3K, HIF-1α, IL-6, and Bcl-2). Oxidative stress markers such as TOS (total oxidant status), SOD (superoxide dismutase) GPx (glutathione peroxidase), and TAS (total antioxidant status) were measured spectrophotometrically, and the oxidative stress index (OSI) was derived to offer an overall oxidative stress measure. Histopathological analysis revealed significant eosinophil infiltration and basement membrane thickening in NP tissues compared to concha bullosa samples. Apoptosis rates were notably higher in concha bullosa tissues. NP tissues showed an upregulation of miR-155-5p and its target genes (PI3K, HIF-1α, IL-6, and Bcl-2). Additionally, NP samples showed an increase in oxidative stress, which was shown by higher TOS and OSI values and lower TAS, suggesting that oxidative imbalance may play a role in NP pathophysiology. Our results suggest that the PI3K/AKT/HIF-1α signaling pathway and miR-155-5p are important for NP production. The observed oxidative stress suggests that targeting both oxidative pathways and miR-155-5p-associated signaling could be beneficial in developing future therapeutic strategies. This study provides novel insights into the molecular underpinnings of NP formation, identifying potential therapeutic targets for improved clinical management.</p>

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The Role of miR-155-5p, PIK3K/AKT/HIF-1α Signaling Pathway, and Oxidative Stress in Nasal Polyp Formation: A Molecular Insight into Potential Therapeutic Targets

  • Muhammet Yusuf TEPEBAŞI,
  • Yusuf Çağdaş KUMBUL,
  • Halil İbrahim BÜYÜKBAYRAM,
  • Hasan YASAN,
  • Melda ŞAHİN

摘要

Nasal polyps (NPs) are benign, inflammatory soft tissue growths in the nasal and paranasal sinus passages that are closely associated with chronic rhinosinusitis (CRS), which has a major influence on patients’ quality of life. This study aimed to investigate the role of miR-155-5p, its target genes, and oxidative stress in the molecular mechanisms driving NP formation. A total of 133 patients, including those with NPs (n = 65) and middle concha bullosa (n = 68), were evaluated via endoscopic examination and computed tomography. Tissue samples were stained with hematoxylin and eosin to examine structural alterations, and TUNEL labeling was used to detect apoptotic cells. Quantitative RT-qPCR was utilized to quantify miR-155-5p and its target genes (PI3K, HIF-1α, IL-6, and Bcl-2). Oxidative stress markers such as TOS (total oxidant status), SOD (superoxide dismutase) GPx (glutathione peroxidase), and TAS (total antioxidant status) were measured spectrophotometrically, and the oxidative stress index (OSI) was derived to offer an overall oxidative stress measure. Histopathological analysis revealed significant eosinophil infiltration and basement membrane thickening in NP tissues compared to concha bullosa samples. Apoptosis rates were notably higher in concha bullosa tissues. NP tissues showed an upregulation of miR-155-5p and its target genes (PI3K, HIF-1α, IL-6, and Bcl-2). Additionally, NP samples showed an increase in oxidative stress, which was shown by higher TOS and OSI values and lower TAS, suggesting that oxidative imbalance may play a role in NP pathophysiology. Our results suggest that the PI3K/AKT/HIF-1α signaling pathway and miR-155-5p are important for NP production. The observed oxidative stress suggests that targeting both oxidative pathways and miR-155-5p-associated signaling could be beneficial in developing future therapeutic strategies. This study provides novel insights into the molecular underpinnings of NP formation, identifying potential therapeutic targets for improved clinical management.