TORONTO: A trial-oriented multidimensional psychometric testing algorithm.

Bayesian adaptive methods for sensory threshold determination were conceived originally to track a single threshold. When applied to the testing of vision, they do not exploit the spatial patterns that underlie thresholds at different locations in the visual field. Exploiting these patterns has been recognized as key to further improving visual field test efficiency. We present a new approach (TORONTO) that outperforms other existing methods in terms of speed and accuracy. TORONTO generalizes the QUEST/ZEST algorithm to estimate simultaneously multiple thresholds. After each trial, without waiting for a fully determined threshold, the trial-oriented approach updates not only the location currently tested but also all other locations based on patterns in a reference data set. Since the availability of reference data can be limited, techniques are developed to overcome this limitation. TORONTO was evaluated using computer-simulated visual field tests: In the reliable condition (false positive [FP] = false negative [FN] = 3%), the median termination and root mean square error (RMSE) of TORONTO was 153 trials and 2.0 dB, twice as fast with equal accuracy as ZEST. In the FP = FN = 15% condition, TORONTO terminated in 151 trials and was 2.2 times faster than ZEST with better RMSE (2.6 vs. 3.7 dB). In the FP = FN = 30% condition, TORONTO achieved 4.2 dB RMSE in 148 trials, while all other techniques had > 6.5 dB RMSE and terminated much slower. In conclusion, TORONTO is a fast and accurate algorithm for determining multiple thresholds under a wide range of reliability and subject conditions.

Metabolomics reveals the potential metabolic mechanism of infliximab against DSS-induced acute and chronic ulcerative colitis.

Inflammatory bowel disease (IBD) is often accompanied by metabolic imbalance, and infliximab (IFX) can alleviate IBD symptoms, but its metabolic mechanisms remain unclear. To investigate the relationship between IBD, metabolism, and IFX, an acute and chronic ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) was established. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis. The results showed that IFX could alleviate colonic shortening and reduce colonic pathological damage in acute and chronic mouse colitis, improve acute and chronic UC, and ameliorate metabolic disturbances. Among the 104 elevated metabolites and 170 decreased metabolites, these metabolites mainly belonged to amino acids, glucose, and purines. The changes in these metabolites were mainly associated with drug metabolism-other enzymes, riboflavin metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phosphonate and phosphinate metabolism, and phenylalanine metabolism. In summary, this study provides a valuable approach to explore the metabolic mechanisms of IFX in treating acute and chronic UC from a metabolomics perspective.

Improving the robustness of the Sequentially Optimized Reconstruction Strategy (SORS) for visual field testing.

Perimetry, or visual field test, estimates differential light sensitivity thresholds across many locations in the visual field (e.g., 54 locations in the 24-2 grid). Recent developments have shown that an entire visual field may be relatively accurately reconstructed from measurements of a subset of these locations using a linear regression model. Here, we show that incorporating a dimensionality reduction layer can improve the robustness of this reconstruction. Specifically, we propose to use principal component analysis to transform the training dataset to a lower dimensional representation and then use this representation to reconstruct the visual field. We named our new reconstruction method the transformed-target principal component regression (TTPCR). When trained on a large dataset, our new method yielded results comparable with the original linear regression method, demonstrating that there is no underfitting associated with parameter reduction. However, when trained on a small dataset, our new method used on average 22% fewer trials to reach the same error. Our results suggest that dimensionality reduction techniques can improve the robustness of visual field testing reconstruction algorithms.

Using Fused Data from Perimetry and Optical Coherence Tomography to Improve the Detection of Visual Field Progression in Glaucoma.

Perimetry and optical coherence tomography (OCT) are both used to monitor glaucoma progression. However, combining these modalities can be a challenge due to differences in data types. To overcome this, we have developed an autoencoder data fusion (AEDF) model to learn compact encoding (AE-fused data) from both perimetry and OCT. The AEDF model, optimized specifically for visual field (VF) progression detection, incorporates an encoding loss to ensure the interpretation of the AE-fused data is similar to VF data while capturing key features from OCT measurements. For model training and evaluation, our study included 2504 longitudinal VF and OCT tests from 140 glaucoma patients. VF progression was determined from linear regression slopes of longitudinal mean deviations. Progression detection with AE-fused data was compared to VF-only data (standard clinical method) as well as data from a Bayesian linear regression (BLR) model. In the initial 2-year follow-up period, AE-fused data achieved a detection F1 score of 0.60 (95% CI: 0.57 to 0.62), significantly outperforming (p < 0.001) the clinical method (0.45, 95% CI: 0.43 to 0.47) and the BLR model (0.48, 95% CI: 0.45 to 0.51). The capacity of the AEDF model to generate clinically interpretable fused data that improves VF progression detection makes it a promising data integration tool in glaucoma management.

ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer.

The pathogenesis of inflammatory bowel disease (IBD) remains unclear and is associated with an increased risk of developing colitis-associated cancer (CAC). Under sustained inflammatory stimulation in the intestines, loss of early DNA damage response genes can lead to tumor formation. Many proteins are involved in the pathways of DNA damage response and play critical roles in protecting genes from various potential damages that DNA may undergo. ERCC4 is a structure-specific endonuclease that participates in the nucleotide excision repair (NER) pathway. The catalytic site of ERCC4 determines the activity of NER and is an indispensable gene in the NER pathway. ERCC4 may be involved in the imbalanced process of DNA damage and repair in IBD-related inflammation and CAC. This article primarily reviews the function of ERCC4 in the DNA repair pathway and discusses its potential role in the processes of IBD-related inflammation and carcinogenesis. Finally, we explore how this knowledge may open novel avenues for the treatment of IBD and IBD-related cancer.

Investigating the effects of a temperature dependent photodynamic dose: A numerical study.

SIGNIFICANCE: Photodynamic therapy (PDT) and photothermal therapy (PTT) show promise as cancer treatments, but challenges in generating large ablative volumes for deep-seated tumours persist. Using simulations, this study investigates combined PDT and PTT to increase treatment volumes, including the impact of a temperature-dependent PDT dose on the treatment volume radius. APPROACH: A finite-element model, using the open-source SfePy package, was developed to simulate combined interstitial photothermal and photodynamic treatments. Results compared an additive dose model to a temperature-dependent dose model with enhanced PDT dosimetry and examined typical clinical scenarios for possible synergistic effects. RESULTS: Findings revealed that the temperature-dependent dose model could significantly expand the damage radius compared to the additive model, depending on the tissue and drug properties. CONCLUSIONS: Characterizing synergistic effects of PDT and PTT could enhance treatment planning. Future work is ongoing to implement additional variables, such as photosensitizer photobleaching, and spatial and temporally varying oxygenation.

A Data-Driven Model for Simulating Longitudinal Visual Field Tests in Glaucoma.

Purpose: To develop a simulation model for glaucomatous longitudinal visual field (VF) tests with controlled progression rates. Methods: Longitudinal VF tests of 1008 eyes from 755 patients with glaucoma were used to learn the statistical characteristics of VF progression. The learned statistics and known anatomic correlations between VF test points were used to automatically generate progression patterns for baseline fields of patients with glaucoma. VF sequences were constructed by adding spatially correlated noise templates to the generated progression patterns. The two one-sided test (TOST) procedure was used to analyze the equivalence between simulated data and data from patients with glaucoma. VF progression detection rates in the simulated VF data were compared to those in patients with glaucoma using mean deviation (MD), cluster, and pointwise trend analysis. Results: VF indices (MD, pattern standard deviation), MD linear regression slopes, and progression detection rates for the simulated and patients' data were practically equivalent (TOST P < 0.01). In patients with glaucoma, the detection rates in 7 years using MD, cluster, and pointwise trend analysis were 24.4%, 26.2%, and 38.4%, respectively. In the simulated data, the mean detection rates (95% confidence interval) for MD, cluster, and pointwise trend analysis were 24.7% (24.1%-25.2%), 24.9% (24.2%-25.5%), and 35.7% (34.9%-36.5%), respectively. Conclusions: A novel simulation model generates glaucomatous VF sequences that are practically equivalent to longitudinal VFs from patients with glaucoma. Translational Relevance: Simulated VF sequences with controlled progression rates can support the evaluation and optimization of methods to detect VF progression and can provide guidance for the interpretation of longitudinal VFs.

Relative efficacy of intracameral moxifloxacin injection methods.

PURPOSE: To determine the amount of moxifloxacin remaining in the anterior chamber (AC), immediately after its injection using 3 current injection methods, assuming mixing and fluid exchange with the AC contents during injection of the drug, and to determine the most desirable injection method. SETTING: Department of Ophthalmology and Vision Sciences and Institute of Biomedical Engineering, University of Toronto, Toronto, Canada. DESIGN: Mathematical modeling. METHODS: Mathematical modeling using first-order mixing methods were used to assess mixing. RESULTS: The Kaiser method of injecting 0.5 mL × 100 µg/0.1 mL does not achieve the desired 500 µg level of moxifloxacin in the AC. The "straight from the bottle" method of injecting 0.1 mL × 500 µg/0.1 mL is fraught with potential error, yielding a relatively unreliable final amount in the AC. Injecting 0.5 to 0.6 mL × 150 µg/0.1 mL yields a result closest to the desired goal. CONCLUSIONS: Based on the calculation, the most accurate of current methods to deliver 500 µg moxifloxacin intracamerally is the method of 150 µg/0.1 mL × 0.5 to 0.6 mL.

Repair of exposure and fracture of the porous high-density polyethylene framework after ear reconstruction.

OBJECTIVE: To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction. STUDY DESIGN: A prospective case study. METHODS: From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient. RESULTS: After follow-up for 3-36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived. CONCLUSION: The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.

Development of a prognostic prediction model based on a combined multi-omics analysis of head and neck squamous cell carcinoma cell pyroptosis-related genes.

This study aimed to understand the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) and to develop and validate a prognostic model for HNSCC based on pyroptosis-associated genes (PAGs) in nasopharyngeal carcinoma. The Cancer Genome Atlas database was used to identify differentially expressed PAGs. These genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes functional annotation analyses and Gene Ontology analyses. The NLR family pyrin domain containing 1 (NLRP1) gene, charged multivesicular body protein 7 (CHMP7) gene, and cytochrome C (CYCS) gene were used to create a prognostic model for HNSCC. The results of the Kaplan-Meier (K-M) and Cox regression analyses indicated that the developed model served as an independent risk factor for HNSCC. According to the K-M analysis, the overall survival of high-risk patients was lower than that of low-risk patients. The hazard ratios corresponding to the risk scores determined using the multivariate and univariate Cox regression analyses were 1.646 (95% confidence interval (CI): 1.189-2.278) and 1.724 (95% CI: 1.294-2.298), respectively, and the area under the receiver operator characteristic curve was 0.621. The potential mechanisms associated with the functions of the identified genes were then identified, and the tumor microenvironment and levels of immune cell infiltration achieved were analyzed. The immune infiltration analysis revealed differences in the distribution of Th cells, tumor-infiltrating lymphocytes, regulatory T cells, follicular helper T cells, adipose-derived cells, interdigitating dendritic cells, CD8+ T cells, and B cells. However, validating bioinformatics analyses through biological experiments is still recommended. This study developed a prognostic model for HNSCC that included NLRP1, CHMP7, and CYCS.

Engineering Bioactive M2 Macrophage-Polarized, Anti-inflammatory, miRNA-Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials.

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during the process of muscle healing, but the detailed mechanism of miRNA-mediated intercellular communication between myoblasts and macrophages remains unclear. Here, it is reported that myoblasts secrete miRNAs-enriched exosomes in the inflammatory environment, through which miR-224 is transferred into macrophages to inhibit M2 polarization. Further data demonstrate that WNT-9a may be a direct target of miR-224 for macrophage polarization. In turn, the secretome of M1 macrophages impairs myogenic differentiation and promotes proliferation. Single-cell integration analysis suggests that the elevation of exosome-derived miR-224 is caused by the activation of the key factor E2F1 in myoblasts and demonstrates the RB/E2F1/miR-224/WNT-9a axis. In vivo results show that treatment with antagomir-224 or liposomes containing miR-224 inhibitors suppresses fibrosis and improves muscle recovery. These findings indicate the importance of the crosstalk between myoblasts and macrophages via miRNA-containing exosomes in the regulation of macrophage polarization and myogenic differentiation/proliferation during muscle healing. This study provides a strategy for treating muscle injury through designing an M2 polarization-enabling anti-inflammatory and miRNA-based bioactive material.

Corrigendum: Three-Dimensional Cartilage Regeneration Using Engineered Cartilage Gel With a 3D-Printed Polycaprolactone Framework.

[This corrects the article DOI: 10.3389/fbioe.2022.871508.].

Three-Dimensional Cartilage Regeneration Using Engineered Cartilage Gel With a 3D-Printed Polycaprolactone Framework.

The feasibility of the three-dimensional (3D) cartilage regeneration technology based on the "steel (framework)-reinforced concrete (engineered cartilage gel, ECG)" concept has been verified in large animals using a decalcified bone matrix (DBM) as the framework. However, the instability of the source, large sample variation, and lack of control over the 3D shape of DBM have greatly hindered clinical translation of this technology. To optimize cartilage regeneration using the ECG-framework model, the current study explores the feasibility of replacing the DBM framework with a 3D-printed polycaprolactone (PCL) framework. The PCL framework showed good biocompatibility with ECG and achieved a high ECG loading efficiency, similar to that of the DBM framework. Furthermore, PCL-ECG constructs caused a milder inflammatory response in vivo than that induced by DBM-ECG constructs, which was further supported by an in vitro macrophage activation experiment. Notably, the PCL-ECG constructs successfully regenerated mature cartilage and essentially maintained their original shape throughout 8 weeks of subcutaneous implantation. Quantitative analysis revealed that the GAG and total collagen contents of the regenerated cartilage in the PCL-ECG group were significantly higher than those in the DBM-ECG group. The results indicated that the 3D-printed PCL framework-a clinically approved biomaterial with multiple advantages including customizable shape design, mechanical strength control, and standardized production-can serve as an excellent framework for supporting the 3D cartilage regeneration of ECG. This provides a feasible novel strategy for the clinical translation of ECG-based 3D cartilage regeneration.

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment.

Cognition may be improved by the active ingredients of the Yiqi Qingre Ziyin method in patients with atrophic rhinitis (AR). This study aimed to identify potential targets of the Yiqi Qingre Ziyin method for the treatment of patients with cognitive impairment. Nasal mucosal tissue samples from patients with AR were subjected to proteomic assays, and differentially expressed proteins were obtained. To explore the mechanism of AR leading to mild cognitive impairment (MCI), a differential analysis of AR related differential proteins in the MCI related GSE140831 dataset was performed. Most AR-related differential proteins are also differentially expressed in peripheral blood tissues of MCI, have similar biological functions and are enriched in similar pathways. These co-expressed differential factors in AR and MCI are known as common differential proteins of AR and MCI (CDPAM). Based on the analysis and validation of the random forest, support vector machine and neural network models, CDPAM acted as a diagnostic marker for MCI risk. Cytochrome C (CYCS) was significantly upregulated in the peripheral blood of patients with MCI. The active ingredients in the Yiqi Qingre Ziqin method were obtained and targeted 137 proteins. Among these targeted proteins, CYCS belong to the CDPAM set. Molecular docking and molecular dynamics analysis revealed that baicalein, an active ingredient in the Yiqi Qingre Ziyin method, stably targeted the CYCS protein. Results of the enrichment analysis revealed that the up-regulation of CYCS expression may have a defensive effect on the cells to resist foreign stimuli. Therefore, baicalein, an active ingredient in the Yiqi Qingre Ziyin method, may prevent the development and progression of MCI by targeting the CYCS protein.

Effects of Endoscopic Sinus Surgery Combined with Budesonide Treatment on Nasal Cavity Function and Serum Inflammatory Factors in Patients with Chronic Sinusitis.

In this article, we have explored the effects of endoscopic sinus surgery together with budesonide treatment on nasal function and serum inflammatory factors on patients with chronic sinusitis. We retrospectively analyzed 120 patients with chronic sinusitis who were admitted to our hospital from March 2018 to March 2021 and were eligible for this study. They were separated into 2 groups according to different treatments, that is, the control group (treated with endoscopic surgery alone) of 58 cases and observation group (treated with endoscopic sinus surgery combined with budesonide) with 62 cases. Treatment efficacy, surgical status, overall symptom score before and after treatment, nasal mucociliary clearance function, serum eosinophils (EOS), serum immunoglobulin E (IgE), serum inflammatory factors, and occurrence of adverse reactions of both groups were recorded and compared. Total effective rate in the observation group presented strikingly more positive compared with that among patients in control group (P<0.05), as well as the data recorded in terms of operation time, blood loss during surgery and postoperative improvement time of patients (P<0.05). Overall symptom score, nasal mucociliary clearance, EOS, IgE and serum inflammatory factors in both groups were improved notably after treatment, while the observation group held a more obvious improvement. And it also had a markedly lower incidence of adverse reaction (P<0.05). Endoscopic sinus surgery combined with budesonide in the treatment of chronic sinusitis could effectively improve the clinical symptoms of patients, reestablish the function of the nasal cavity and improve their inflammation level. Meanwhile, it was of high safety and is worthy of clinical promotion.

Exploring the Mechanism of Yiqi Qingre Ziyin Method in Regulating Neuropeptide Expression for the Treatment of Atrophic Rhinitis.

Atrophic rhinitis (AR) is a chronic disease that causes severe structural changes to the nasal mucosa leading to squamous epithelial metaplasia. However, treatment regarding AR remains a major challenge. We used network pharmacology and molecular docking methods to explore the potential mechanisms of the Yiqi Qingre Ziyin method to modulate neuropeptides in the treatment of AR. The active ingredients of the Yiqi Qingre Ziyin method and their targets of action were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database Analysis Platform (TCMSP). Disease targets for AR were obtained from four databases: GeneCards, PharmGKB, DrugBank, and Online Mendelian Inheritance in Man (OMIM). A total of 59 active ingredients, 39 potential targets, and 76 relevant neuropeptides were obtained after deduplication. We constructed target interaction networks with the STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the 14 potential target proteins. We used Cytoscape software to construct the "drug-active ingredient-potential target" and "ingredient-target-pathway" networks of the Yiqi Qingre Ziyin method for treating AR. Molecular docking results suggest that dipeptidyl peptidase 4 (DPP4), opioid receptor gene d1 (OPRD1), and opioid receptor m1 (OPRM1) are key targets for the Yiqi Qingre Ziyin method. Therefore, this study proposed a potential mechanism for the treatment of AR by affecting the expression of neuropeptide-related genes (including DPP4, OPRD1, and OPRM1), which may potentially improve the immune microenvironment of the nasal mucosa.

Multicenter Comparison of the Toronto Portable Perimeter with the Humphrey Field Analyzer: A Pilot Study.

PURPOSE: To evaluate the agreement between glaucomatous 24-2 visual field (VF) testing performed with the Toronto Portable Perimeter (TPP; VEM Medical Technologies) and the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec). DESIGN: Multicenter prospective cohort analysis. PARTICIPANTS: Patients with suspected or confirmed glaucoma treated at Prism Eye Institute (Oakville, Canada), York Finch Eye Associates (North York, Canada), or the Ontario Mobile Medical Eye Care Unit (Cochrane, Canada) between March 2019 and March 2020. METHODS: Patients underwent consecutive VF tests on the same eye using the HFA Swedish Interactive Threshold Algorithm Standard 24-2 test and TPP Standard 24-2 test in randomized order. Bland-Altman analysis and paired t tests were used to compare VF results obtained by the TPP and the HFA. Participants completed a 5-question validated questionnaire after completing both testing methods. MAIN OUTCOME MEASURES: Mean difference and degree of agreement in mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and test duration between VF modalities. RESULTS: One hundred fifty eyes from 91 patients were included in analysis. Average MD of the overall cohort using HFA and TPP VF testing was -4.32 ± 5.47 dB and -4.53 ± 5.22 dB, respectively (P = 0.74). Bland-Altman analysis showed good agreement between HFA and TPP tests. The mean differences (95% limits of agreement) between HFA and TPP for MD, PSD, VFI, and test duration were 0.21 dB (-4.25 to 4.67 dB), -0.13 dB (-3.72 to 3.47 dB), 0.66% (-10.94% to 12.26%), and 0.65 seconds (-97.51 to 98.81 seconds), respectively. No statistically significant mean difference was found between HFA and TPP tests for MD, PSD, VFI, or test duration. Mean deviation (R2 = 0.830) and VFI (R2 = 0.866) were correlated strongly with both modalities. Questionnaire results demonstrated that patients significantly preferred the TPP over the HFA for VF testing (P < 0.001). CONCLUSIONS: Mean deviation, PSD, and VFI outcomes measured by the TPP were statistically similar to corresponding parameters obtained with the HFA. Test time duration did not differ significantly between the TPP and HFA, and patients significantly preferred the TPP to the HFA examination experience. These pilot results suggest that the TPP may offer an accessible alternative to HFA VF testing.

An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes.

The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics.

LncRNA SNHG16 Facilitates Nasopharyngeal Carcinoma Progression by Acting as ceRNA to Sponge miR-520a-3p and Upregulate MAPK1 Expression.

BACKGROUND: Accumulating evidence shows that lncRNAs are widely involved cellular processes of various tumors. The aim of this study was to explore the potential role and molecular mechanism of lncRNA SNHG16 in nasopharyngeal carcinoma (NPC). METHODS: SNHG16, miR-520a-3p, and MAPK1 levels were measured by RT-qPCR assay. CCK-8, colony formation, transwell, and flow cytometry assays were adopted to analyze the proliferation, migration, invasion, and apoptosis of NPC cell lines (SUNE1 and 5-8F). Murine xenograft model was used to investigate tumor growth and metastasis in vivo. Immunohistochemical staining was employed to evaluate the levels of Bcl-2, cleaved caspase-3, Bax, and Ki-67. Dual-luciferase reporter assays were conducted to analyze the binding ability between miR-520a-3p and SNHG16 or MAPK1. RESULTS: SNHG16 was overexpressed in NPC tissues and cells. High SNHG16 expression indicated a poor prognosis. SNHG16 knockdown could cause significant inhibition on cell proliferation and metastasis, induce cell apoptosis in NPC cells, and repressed tumor growth and metastasis in vivo. Additionally, SNHG16 could directly bind to miR-520a-3p, thus positively regulating MAPK1 expression. Moreover, functional analysis indicated that miR-520a-3p exerted a tumor-suppressing role in NPC progression. Rescue assays demonstrated that MAPK1 upregulation could abrogate the inhibitory effects on NPC cell proliferation and metastasis, as well as the promoting effects on NPC cell apoptosis caused by SNHG16 knockdown. In conclusion, SNHG16 contributed to the proliferation and metastasis of NPC cells by modulating the miR-520a-3p/MAPK1 axis. CONCLUSION: These results suggest that SNHG16 acts as an oncogene in the progression of NPC via modulating the miR-520a-3p/MAPK1 axis.