ENAH transcriptionally activated by YY1 promotes growth and invasion of laryngocarcinoma cells through PI3K/AKT signaling.

BACKGROUND: Laryngocarcinoma is a common malignancy in the upper respiratory tract. Enabled homolog (ENAH) is an actin-binding protein that is associated with the development of various cancers. However, its role and mechanism in laryngocarcinoma remain unknown. METHODS: The ENAH level in laryngocarcinoma was examined in silico, in vitro and in vivo. The prognostic analysis of the ENAH level was assessed on laryngocarcinoma patients. Gain- and loss-of-function assays were conducted in AMC-HN-8 and TU686 cells. Sh-ENAH-containing AMC-HN-8 cells were implanted into naked mice. The role and mechanism of ENAH in laryngocarcinoma were investigated by CCK-8, transwell, immunofluorescence, dual luciferase, RT-qPCR, immunohistochemistry, and western blotting experiments. RESULTS: The ENAH level was upregulated in laryngocarcinoma, which predicted a poor prognosis in laryngocarcinoma patients. Gain- and loss-of-function results showed that ENAH promoted proliferation, invasion and EMT of laryngocarcinoma cells. Moreover, ENAH was transcriptionally activated by YY1, and YY1/ENAH axis enhanced these malignant progresses of laryngocarcinoma cells. Besides, ENAH activated the PI3K/AKT pathway, and 740Y-P abolished the accelerative role of ENAH in proliferation, invasion and EMT of laryngocarcinoma cells. Furthermore, knockdown of ENAH reduced tumor size and weight, and the expression level of vimentin and PI3K/AKT pathway in tumor-bearing mice. CONCLUSION: ENAH transcriptionally activated by YY1 promotes cell growth, invasion and EMT of laryngocarcinoma through the activation of PI3K/AKT signaling.

lncRNA FLJ20021 regulates CDK1-mediated PANoptosis in a ZBP1-dependent manner to increase the sensitivity of laryngeal cancer-resistant cells to cisplatin.

In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.

Correlation of acoustic voice analysis and Voice Handicap Index in patients with postoperative unilateral vocal cord paralysis after thyroid surgery.

Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.

A Clinical Study on Video Bronchoscopy-guided Coblation for Benign Central Airway Stenosis.

Background: Benign central airway stenosis poses a significant challenge to respiratory and thoracic surgeons due to the high recurrence rate associated with current treatment methods, causing severe breathing difficulties and potentially life-threatening complications. This article aims to investigate the therapeutic efficacy and prospects of using coblation in the management of benign central airway stenosis in adults. Moreover, the pathogenesis of benign central airway stenosis was deeply explored to provide better guidance for future clinical treatments. Materials and Methods: This retrospective study examined patients with benign central airway stenosis who were treated at The Second Hospital of Hebei Medical University from 2017 to 2020. In addition, a comparative analysis of whole-genome sequencing was conducted between the aforementioned patient group and healthy populations to investigate the underlying etiology of this stenotic condition. Results: The present study encompassed 32 patients who underwent 43 treatments in total between 2017 and 2020. All patients exhibited alleviation of airway stenosis and an improvement in clinical symptoms following surgery, without any significant surgical or postoperative complications. Whole-genome analysis revealed significant changes in gene expression in the airway mucosa of patients with benign airway stenosis in comparison to healthy populations. A total of 91 differentially expressed genes were identified, among which 44 upregulated genes displayed characteristics of promoting inflammatory responses. Conclusion: Coblation demonstrates promise as an efficacious treatment modality for adults suffering from benign central airway stenosis, and its widespread application in clinical settings is anticipated. The direct pathogenesis of benign central airway stenosis involves airway lumen narrowing and obstruction resulting from excessive inflammation and proliferative granulation.

Correlation of acoustic voice analysis and Voice Handicap Index in patients with postoperative unilateral vocal cord paralysis after thyroid surgery

Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.

MiR-5189-3p Suppresses cell Proliferation, Invasion and Migration Through Targeting EIF5A2 in Laryngeal Squamous Cell Carcinoma.

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC.

Predicting cervical lymph node metastasis in OSCC based on computed tomography imaging genomics.

BACKGROUND: To investigate the correlation between computed tomography (CT) radiomic characteristics and key genes for cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC). METHODS: The region of interest was annotated at the edge of the primary tumor on enhanced CT images from 140 patients with OSCC and obtained radiomic features. Ribonucleic acid (RNA) sequencing was performed on pathological sections from 20 patients. the DESeq software package was used to compare differential gene expression between groups. Weighted gene co-expression network analysis was used to construct co-expressed gene modules, and the KEGG and GO databases were used for pathway enrichment analysis of key gene modules. Finally, Pearson correlation coefficients were calculated between key genes of enriched pathways and radiomic features. RESULTS: Four hundred and eighty radiomic features were extracted from enhanced CT images of 140 patients; seven of these correlated significantly with cervical LNM in OSCC (p < 0.01). A total of 3527 differentially expressed RNAs were screened from RNA sequencing data of 20 cases. original_glrlm_RunVariance showed significant positive correlation with most long noncoding RNAs. CONCLUSIONS: OSCC cervical LNM is related to the salivary hair bump signaling pathway and biological process. Original_glrlm_RunVariance correlated with LNM and most differentially expressed long noncoding RNAs.

Prediction of 5-year overall survival of tongue cancer based machine learning.

OBJECTIVE: We aimed to develop a 5-year overall survival prediction model for patients with oral tongue squamous cell carcinoma based on machine learning methods. SUBJECTS AND METHODS: The data were obtained from electronic medical records of 224 OTSCC patients at the PLA General Hospital. A five-year overall survival prediction model was constructed using logistic regression, Support Vector Machines, Decision Tree, Random Forest, Extreme Gradient Boosting, and Light Gradient Boosting Machine. Model performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic curve. The output of the optimal model was explained using the Python package (SHapley Additive exPlanations, SHAP). RESULTS: After passing through the grid search and secondary modeling, the Light Gradient Boosting Machine was the best prediction model (AUC = 0.860). As explained by SHapley Additive exPlanations, N-stage, age, systemic inflammation response index, positive lymph nodes, plasma fibrinogen, lymphocyte-to-monocyte ratio, neutrophil percentage, and T-stage could perform a 5-year overall survival prediction for OTSCC. The 5-year survival rate was 42%. CONCLUSION: The Light Gradient Boosting Machine prediction model predicted 5-year overall survival in OTSCC patients, and this predictive tool has potential prognostic implications for patients with OTSCC.

Exosome miR-552 Promotes Laryngocarcinoma Cells Malignant Progression via the PTEN/TOB1 Axis.

INTRODUCTION: Tumor exosome-derived miRNAs play important roles in the human laryngocarcinoma. However, it is still unknown if exosome miR-552 is involved in the laryngocarcinoma. The aim of the current study was to explore exosome miR-552's role in laryngocarcinoma and its underlying mechanisms. METHODS: Hep-2 exosome was characterized by transmission electron microscopy and nanoparticle tracking technology. CCK-8 was used to determine cell viability, and a xenograft animal model was used to determine the tumorigenicity. qPCR and Western blotting were used to measure the changes in target biomarkers. Luciferase reporter assay was used to evaluate the interactions between miR-552 and PTEN. miRNA sequencing was used to check the changes in miRNA profiles. RESULTS: miR-552 was upregulated in the laryngocarcinoma patients and was positively correlated to the cell proliferation and tumor growth. PTEN was identified as a direct target of miR-552. Hep-2 exosome is featured by high expression of miR-552 and treatment of Hep-2 exosome enhanced cell proliferation and tumorigenicity. The underlying mechanisms revealed that treatment of exosomes enhanced the malignant transformation of recipient cells in part by regulating epithelial-mesenchymal transition. CONCLUSION: Exosome miR-552 promotes laryngocarcinoma cells' malignant progression in part by the regulation of the PTEN/TOB1 axis.

Single-cell transcriptomic analysis of the tumor ecosystem of adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a malignant tumor that originates from exocrine gland epithelial cells. We profiled the transcriptomes of 49,948 cells from paracarcinoma and carcinoma tissues of three patients using single-cell RNA sequencing. Three main types of the epithelial cells were identified into myoepithelial-like cells, intercalated duct-like cells, and duct-like cells by marker genes. And part of intercalated duct-like cells with special copy number variations which altered with MYB family gene and EN1 transcriptomes were identified as premalignant cells. Developmental pseudo-time analysis showed that the premalignant cells eventually transformed into malignant cells. Furthermore, MYB and MYBL1 were found to belong to two different gene modules and were expressed in a mutually exclusive manner. The two gene modules drove ACC progression into different directions. Our findings provide novel evidence to explain the high recurrence rate of ACC and its characteristic biological behavior.

Oxaliplatin Induces Immunogenic Cell Death in Human and Murine Laryngeal Cancer.

Background: Cisplatin resistance is observed in patients with laryngeal cancer. The present study was designed to explore the efficacy of oxaliplatin on laryngeal cancer and elucidate the underlying mechanisms. Methods: Cell viability was determined by using MTT assays. Cell apoptosis was determined by using annexin V and propidium iodide (PI) staining. Flow cytometry and immunofluorescence were applied to determine the levels of calreticulin (CALR) and DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). Flow cytometry was applied to analyze the levels of CD83, CD86, IFN-γ-producing CD8+ T cells, and CD4+CD25+FoxP3+ Tregs. The levels of adenosine triphosphate (ATP) were determined by using a chemiluminescent ATP kit and cytokines were determined by using specific enzyme-linked immunosorbent assays (ELISAs). The levels of HMGB1 were determined by using Western blot and ELISA, respectively. The xenograft animal model was constructed to evaluate the antitumor effects of oxaliplatin. Results: Oxaliplatin inhibited cell growth, promoted cell apoptosis, and induced the levels of CALR, ATP, and high mobility group box protein 1 (HMGB1) in Hep-2 cells. Oxaliplatin-treated Hep-2 cells increased the intensity of DiD and the levels of CD83 and CD86 in dendritic cells (DCs), as well as induced the supernatant IL-6 and TNF-α. Oxaliplatin-treated primary laryngeal cancer cell-pulsed DCs increased the IFN-γ-producing CD8+ T cells and suppressed CD4+CD25+FoxP3+ Tregs. In vivo data showed that oxaliplatin suppressed tumor growth and increased the populations of CD86+CD80+ and CD8+CD45+ cells in the tumor tissues. Conclusion: Treatment with oxaliplatin inhibited laryngeal cancer cells by inducing immunogenic cell death.

Medial Epicanthoplasty With the Classic and Modified Skin Redraping Method: A Retrospective Case Control Study.

ABSTRACT: The skin redraping method for medial epicanthoplasty is characterized by some shortcomings which warrants modification. In this study, clinical data of 193 patients who underwent medial epichanthoplasty by the modified skin redraping technique or the classic skin redraping technique were reviewed retrospectively. The patients underwent operation between May 2018 and June 2020 and were followed up for not less than 6 months. Interepicanthal distance, interpupillary distance, patient satisfaction, and postoperative complications were evaluated. In terms of interepicanthal distance/inter-pupillary distance ratio (P > 0.05) and satisfaction score (P = 0.759), the modified skin redraping technique and the classic skin redraping technique were similar. In the classic skin redraping group, there were 3 cases of visible scarring in the lower eyelid, corresponding to significantly more cases than in the modified skin redraping group (n = 0, P < 0.001). There were more out-fold cases in the modified skin redraping group (76/90) than in the classic skin redraping group (17/88) (P < 0.001). Utilizing the modified skin redraping medial epicanthoplasty can prevent medial hooding of the upper eyelid, reduce the probability of visible scarring, and produce more out-fold with concurrent double eyelidplasty compared with classic skin redraping epicanthoplasty. Level of evidence: IV.

Predictive value of systemic inflammatory response-related indices for survival in tongue cancer.

OBJECTIVES: We assessed the potential prognostic significance of the preoperative systemic inflammation index, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio in patients who underwent surgical resection. SUBJECTS AND METHODS: This retrospective study included 224 patients with clinicopathologically confirmed squamous carcinoma of the tongue who underwent surgery between August 2009 and December 2017. The optimal cut-off values for the indices were determined by receiver operating characteristic curves. Correlations between the indices and clinicopathological variables were determined by Pearson chi-square or Fisher exact tests. The Kaplan-Meier test was used to compare overall survival between groups (high and low values); the log-rank or Breslow test was used to assess differences in survival. Univariate and multivariate Cox regression models were used to analyze predictive values of the indices as independent indicators of overall survival. Bilateral p values of <0.05 were considered statistically significant. RESULTS: Significant association was found between the indices and sex, tissue grade, tumor location, and lymph nodes metastases (p < 0.05). On Kaplan-Meier analysis, patients with lower values of the indices had longer overall survival (p < 0.05). Univariate and multivariate Cox regression models identified age, lymph node metastases, and neutrophil-to-lymphocyte ratio as independent predictors of overall survival. CONCLUSION: The studied indices have potential prognostic significance in patients with squamous tongue cancer.

Comprehensive Analysis of LINC01615 in Head and Neck Squamous Cell Carcinoma: A Hub Biomarker Identified by Machine Learning and Experimental Validation.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, but in clinical practice, the lack of precise biomarkers often results in an advanced diagnosis. Hence, it is crucial to explore novel biomarkers to improve the clinical outcome of HNSCC patients. Methods: We downloaded RNA-seq data consisting of 502 HNSCC tissues and 44 normal tissues from the TCGA database, and lncRNA genomic sequence information was downloaded from the GENECODE database for annotating lncRNA expression profiles. We used Cox regression analysis to screen prognostic lncRNAs, the threshold as HR >1 and p value <0.05. Subsequently, three survival outcomes (overall survival, progress-free interval, and disease-specific survival)-related lncRNAs overlapped to get the common lncRNAs. The hub biomarker was identified using LASSO and random forest models. Subsequently, we used a variety of statistical methods to validate the prognostic ability of the hub marker. In addition, Spearman correlation analysis between the hub marker expression and genomic heterogeneity was conducted, such as instability (MSI), homologous recombination deficiency (HRD), and tumor mutational burden (TMB). Finally, we used enrichment analysis, ssGSEA, and ESTIMATE algorithms to explore the changes in the underlying immune-related pathway and function. Finally, the MTT assay and transwell assay were performed to determine the effect of LINC01615 silencing on tumor cell proliferation, invasion, and migration. Results: Cox regression analysis revealed 133 lncRNAs with multiple prognostic significance. The machine learning algorithm screened out the hub lncRNA with the highest importance in the RF model: LINC01615. Clinical correlation analysis revealed that the LINC01615 increased with increasing the T stage, N stage, pathology grade, and clinical stage. LINC01615 could be used as a predictor of HNSCC prognosis validating by a variety of statistical methods. Subsequently, when clinical indicators were combined with the LINC01615 expression, the visualization model (nomogram) was more applicable to clinical practice. Finally, immune algorithms indicated that LINC01615 may be involved in the regulation of lymphocyte recruitment and immunological infiltration in HNSCC, and the LINC01615 expression represented genomic heterogeneity in pan-cancer. Functionally, silencing of LINC01615 suppresses cell proliferation, invasion, and migration in HEP-2 and TU212 cells. Conclusion: LINC01615 may play an important role in the prostromal cell enrichment and immunosuppressive state and serve as a prognostic biomarker in HNSCC.

CAPRIN1 Enhances Chemoresistance and Glycolysis in Laryngeal Squamous Cell Carcinoma via Regulation of ZIC5.

Background: Cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1) plays an important role in carcinogenesis, whereas its role in laryngeal squamous cell carcinoma remains unclear. This study was designed to investigate the roles of CAPRIN1 in glycolysis and chemoresistance and its underlying mechanisms in laryngeal squamous cell carcinoma. Methods: Cell viability was evaluated by using CCK-8 and colony formation assays. qRT-PCR, Western blotting, and immunohistochemistry were used to determine the expressions of target genes. Gene knockdown and overexpression cell lines were constructed by performing transfection of siRNAs and plasmids, respectively. Luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assays were applied to evaluate the RNA-protein interactions. The Kaplan-Meier analysis was performed to evaluate the relationship between gene expression and overall survival rate. Results: An elevation of CAPRIN1 was identified to be associated with chemoresistance and poor prognosis in patients with laryngeal cancer. The increase of CAPRIN1 promoted glycolysis and chemoresistance, whereas the knockdown of CAPRIN1 inhibited glycolysis and chemoresistance in laryngeal cancer cells. The underlying mechanistic investigation revealed that CAPRIN1 promoted glycolysis and chemoresistance of laryngeal cancer cells by the regulation of Zic Family Member 5 (ZIC5). Conclusion: CAPRIN1 promoted laryngeal squamous cell carcinoma glycolysis and chemoresistance by the regulation of ZIC5.

Clinical Response to Neoadjuvant Immunotherapy Combined with Targeted Therapy and Chemotherapy in Oral Squamous Cell Carcinoma: Experience in Three Patients.

Immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab have been approved for the treatment of head and neck squamous cell carcinoma (HNSCC) and used in neoadjuvant immunotherapy in clinical trials. However, combination of ICIs with targeted therapy and chemotherapy was rarely used in pre-surgical HNSCC patients. Herein, we encountered three cases of patients with oral squamous cell carcinoma (OSCC) who all had good responses to neoadjuvant immunotherapy (anti-PD-1 inhibitors) combined with nimotuzumab (anti-EGFR monoclonal antibody) plus paclitaxel. Both Case 1 and Case 2 underwent the same neoadjuvant therapeutic combination (nivolumab, nimotuzumab and paclitaxel) and exhibited a marked tumor shrinkage even complete disappearance by radiological evaluation. Moreover, pathological response was observed in post-surgical tissues of Case 1. Additionally, Case 3 with tongue squamous cell carcinoma also had satisfactory tumor regression (complete healing of his tongue ulcer upon treatment) after receiving similar neoadjuvant therapy with sintilimab (another PD-1 inhibitor), nimotuzumab and paclitaxel. We characterized their potential causes behind favorable treatment outcomes. While there were differences in driver mutations and tumor mutation burden (TMB) identified in pre-treatment tumor tissues among the three patients, numerous CD68+ (macrophages) infiltrates were common for all the cases. Of note, the majority (>80%) of the total macrophages were molecularly defined as PD-L1-positive macrophages. Given the high expression of PD-L1 in macrophages is associated with better immunotherapy outcomes, we propose that the high proportion of CD68+PD-L1+ cells in total macrophages alone could serve as a promising biomarker for neoadjuvant immunotherapy in combination with other therapies in HNSCC.

Novel fluorescent GLUT1 inhibitor for precision detection and fluorescence image-guided surgery in oral squamous cell carcinoma.

Early detection and complete resection of oral squamous cell carcinoma (OSCC) are crucial to improving patient survival and prognosis. However, specifically targeted imaging probes for OSCC detection are limited. Our study aimed to synthesize a novel near-infrared fluorescence (NIRF) probe for precision detection and fluorescence image-guided surgery in OSCC. Bioinformatics data indicated that glucose transporter 1 (GLUT1) is highly expressed in patients with OSCC. We demonstrated high and specific GLUT1 expression upon immunohistochemical staining of samples from 20 patients with OSCC. The specific expression of GLUT1 was further validated in both human OSCC cell lines and OSCC tumor xenografts. Based on these findings, the GLUT1 inhibitor WZB117 was utilized to synthesize a novel NIRF imaging probe, WZB117-IR820. The fluorescence molecular imaging data revealed that WZB117-IR820 could specifically bind to the tumor areas in an orthotopic OSCC mouse model after intravenous injection and could be further applied for precision fluorescence image-guided surgery with no residual tumor in the orthotopic CAL27-fLUC mouse tumor model. For further clinical translational application in patients with OSCC, precise delineation of OSCC tumor areas was achieved after topical application of the WZB117-IR820 imaging probe and was validated by histopathological and immunohistochemical analyses. In conclusion, we synthesized a novel fluorescent imaging probe, WZB117-IR820, which has potential clinical applications for early detection and fluorescence image-guided surgery in OSCC with no observable toxicity.

Circular RNA ZNF609 promotes laryngeal squamous cell carcinoma progression by upregulating epidermal growth factor receptor via sponging microRNA-134-5p.

Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. CircZNF609 was found to be involved in hepatocellular carcinoma, but the role and underlying mechanism of circZNF609 in laryngeal squamous cell carcinoma (LSCC) remain unclear. This study aimed to explore the molecular mechanism of circZNF609 in LSCC. qRT-qPCR was performed to detect the expression of circZNF609 and microRNA-134-5p (miR-134-5p) in LSCC. Colony formation assay, CCK-8 assay, BrdU incorporation assay, clone formation assay, transwell invasion assay and Western blot analysis were performed to evaluate LSCC cell proliferation, as well as the expression of proliferating cell nuclear antigen (PCNA) and MMP-2. Luciferase reporter assay, target gene prediction and screening were used to validate downstream target genes of circZNF609 and miR-134-5p. EGFR expression was detected by Western blot analysis and RT-qPCR. Nude mice were used to detect tumor changes. CircZNF609 was upregulated in LSCC and associated with poor survival of LSCC patients. Knockdown of circZNF609 inhibited LSCC proliferation, invasion and the expression of PCNA and matrix matalloproteinases-2 (MMP-2). CircZNF609 can regulate miR-134-5p to upregulate epidermal growth factor receptor (EGFR). In addition, knockdown of EGFR or overexpression of miR-134-5p could reverse the tumor-promoting effects of circZNF609 in LSCC. In LSCC tissues, circZNF609 was negatively correlated with miR-134-5p and positively correlated with EGFR. CircZNF609 promotes the progression of LSCC via the miR-134-5p/EGFR axis, which might be the therapeutic target of LSCC.

Anti-CD47 antibody synergizes with cisplatin against laryngeal cancer by enhancing phagocytic ability of macrophages.

Cisplatin is mainly used in late-stage or recurrent laryngeal cancer patients. However, the effect of the chemotherapy is limited due to cisplatin resistance. Therefore, we explored the synergized role of immunosuppressive mediator with cisplatin in laryngeal cancer. Cancer cells isolated from tissues of patients with laryngeal cancer were treated with cisplatin to screen the potential immunosuppressive mediator, whose synergized effects with cisplatin were explored both in vivo and in vitro. CD47 was selected for its high expression in cisplatin-treated laryngeal cancer cells. Blocking CD47 expression using its neutralizing antibody (aCD47) synergized with cisplatin to increase macrophage phagocytosis in a co-culture system of human epithelial type 2 (Hep-2) cancer cells with tumor-associated macrophages (TAMs). Moreover, aCD47 together with cisplatin prevented tumor growth by inhibiting proliferation of cancer cells and the secretion of proinflammatory cytokines, as well as by inducing the apoptosis of cancer cells and phagocytosis of TAMs in a Hep-2-implanted mouse tumor model. aCD47 synergized with cisplatin against laryngeal cancer by enhancing the phagocytic ability of TAMs, and the combined therapy of cisplatin and aCD47 might serve as a novel therapeutic strategy against laryngeal cancer.

Knockdown of LncRNA PANDAR by CRISPR-dCas9 Decreases Proliferation and Increases Apoptosis in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial tumor in the oral cavity. Emerging evidence has demonstrated the important function roles of long noncoding RNAs (lncRNAs) in human cancers. LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) functions as an oncogene in multiple carcinomas, whereas its function in OSCC has not been investigated yet. The aim of our study is to investigate the possible regulatory mechanism of PANDAR in OSCC. First of all, PANDAR was highly expressed in OSCC cells and loss-of-function assays mediated by CRISPR-dCas9 observed that PANDAR silencing restrained cell proliferation and promoted cell apoptosis. Then we found and confirmed the interaction between PANDAR and serine and arginine rich splicing factor 7 (SRSF7). Subsequently, serine/threonine-protein kinase pim-1 (PIM1) was proved to be regulated by PANDAR in SRSF7-dependant way. Rescue experiments validated that PANDAR modulated the proliferation and apoptosis in OSCC through PIM1. In conclusion, PANDAR bound with SRSF7 to increase PIM1 expression, hence promoting the development of OSCC. These data shed new lights into the seeking for effective diagnostic biomarkers and therapeutic targets for OSCC patients.