Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop.
Molecular cancer
BACKGROUND:Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). METHODS:The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and β-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between β-TrCP and c-Myc in NPC cells. RESULTS:We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to β-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. CONCLUSIONS:Our results revealed the important role of circPVT1 in the progression of NPC through the β-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC.
10.1186/s12943-022-01659-w
Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis.
Nature immunology
The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15 macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (T2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.
10.1038/s41590-022-01312-0
A comparative study of transcervical, endoscope-assisted transcervical, and endoscope-assisted transoral resection of retrostyloid space schwannomas.
Head & neck
BACKGROUND:The aim of this retrospective study was to compare the efficacy of transcervical (TC), endoscope-assisted transoral (TO), and endoscope-assisted TC for resection of retrostyloid space schwannomas. METHODS:The study included patients who underwent complete resection of schwannomas by only one surgical approach. The data we collected included tumor size, estimated blood loss, postoperative complications, and so on. Statistical analysis was performed using one-way analysis of variance and Fisher's exact test. RESULTS:The study collected 85 patients with tumors mostly located at the oropharyngeal level who were followed up 6 months at least. The results showed that endoscope-assisted TO had certain advantages over others. Additionally, the endoscope-assisted TO set the lowest incidence of neurological complications. CONCLUSION:Our findings demonstrate that for team with rich experience in the skull base surgery, endoscope-assisted TO is a superior option compared to the other two groups for resection of retrostyloid space schwannomas, with the better preservation of neurological function.
10.1002/hed.27829
Unveiling the Impact of Smoking on Allergic Rhinitis: Disease Severity and Efficacy of Subcutaneous Immunotherapy.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
OBJECTIVE:To evaluate the impact of smoking statuses on disease severity and subcutaneous immunotherapy (SCIT) efficacy in allergic rhinitis (AR). STUDY DESIGN:Open observational cohort study. SETTING:Tertiary referral center. METHODS:Five hundred and five AR patients undergoing dust mite allergen SCIT were categorized into never smokers, former smokers, and current smokers. AR severity was assessed using widely employed questionnaires. The changes in questionnaire scores pre- and post-SCIT were evaluated for SCIT efficacy. The differences in disease severity and SCIT efficacy were compared for different smoking statuses among AR patients. RESULTS:Compared to never smokers, former and current smokers exhibited higher proportion of male, alcohol, and asthma (P < .05). Current smokers had a greater prevalence of allergic conjunctivitis than former smokers (P < .05). Before SCIT, AR severity was similar across 3 groups, even after adjusting for confounders (P > .05). Current smokers reported lower SCIT efficacy in the first year (P < .05). By the third year, 3 groups showed comparable long-term efficacy (P > .05). However, current smokers experienced a significant decrease in benefits 2 years post-SCIT (P < .05) and lower improvement rates at the end of the 3-years SCIT period and 2 years following SCIT (P < .05). CONCLUSION:AR patients across different smoking statuses demonstrated similar baseline disease severity and long-time SCIT efficacy. Active smoking was associated with increased asthma risk, delayed early SCIT efficacy perception, reduced improvement over 3 years, and diminished benefits 2 years after SCIT. Prompt smoking cessation is crucial to mitigate these effects.
10.1002/ohn.937
Combining single-cell spatial transcriptomics and molecular simulation to develop in vivo probes targeting the perineural invasion region of adenoid cystic carcinoma.
Heliyon
Background and objectives:Perineural invasion (PNI) refers to the invasion, encasement, or penetration of tumor cells around or through nerves. Various malignant tumors, including pancreatic cancer, head and neck tumors, and bile duct cancer, exhibit the characteristic of PNI. Particularly, in head and neck-skull base tumors such as adenoid cystic carcinoma (ACC), PNI is a significant factor leading to incomplete surgical resection and postoperative recurrence. Methods:Spatial transcriptomic and single-cell transcriptomic sequencing were conducted on a case of ACC tissue with PNI to identify potential probes targeting PNI. The efficacy of the probes was validated through in vivo and in vitro experiments. Results:Spatial transcriptomic and single-cell RNA sequencing revealed phenotypic changes in Schwann cells within the PNI region of ACC. Peptide probes were designed based on the antigen-presenting characteristics of Schwann cells in the PNI region, which are dependent on Major Histocompatibility Complex II (MHC-II) molecules. Successful validation in vitro and in vivo experiments confirmed that these probes can label viable Schwann cells in the PNI region, serving as a tool for dynamic in vivo marking of tumor invasion into nerves. Conclusions:Peptide probes targeting Schwann cells' MHC-II molecules have the potential to demonstrate the occurrence of PNI in patients with ACC.
10.1016/j.heliyon.2024.e34628
NOX2 mediates NLRP3/ROS facilitating nasal mucosal epithelial inflammation in chronic rhinosinusitis with nasal polyps.
Heliyon
Background:Previous investigations have provided limited insight into the role of oxidative stress in nasal mucosa inflammation. The aim of this study was to investigate the mechanism of oxidative stress in the epithelial cells of chronic rhinosinusitis with nasal polyps CRSwNP utilizing single-cell RNA sequencing data. Methods:Single-cell RNA sequencing data from HRA000772 were used to assess oxidative stress, inflammasome activation, and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) expression in epithelial cells via integrative rank-based gene set enrichment analysis. The localization of reactive oxygen species (ROS) and NOX2 in nasal mucosa and cell models was visualized using fluorescent probes and immunohistochemistry, respectively. Functional studies on NOX2 involved siRNA and plasmid transfections , while Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity was examined using the inducer TMAO and the inhibitor MCC950. Results:Single-cell RNA sequencing data suggested an increase of oxidative stress score and NLRP3 inflammasome score in CRSwNP epithelial cells. Vitro experiments demonstrated that lipopolysaccharide could induce ROS accumulation, NLRP3 inflammasome activation and epithelial alarmin expression. MCC950 inhibited the expression of epithelia alarmin . Elevated NOX2 in CRSwNP epithelial cells was associated with increased ROS, NLRP3 inflammasome activation, and epithelial alarmin expression. NOX2-targeted siRNA inhibited these effects . Moreover, TMAO reversed the downregulation of epithelial alarmins without impacting ROS levels. Conclusion:This study highlights the crucial role of NOX2 as a key regulator of ROS accumulation and NLRP3 inflammasome activation in CRSwNP, underscoring its potential as a valuable therapeutic target for CRSwNP.
10.1016/j.heliyon.2024.e38029