Introduction: Antidifferentiation noncoding RNA (ANCR) is a newly identified long noncoding RNA, which is reported to function as an oncogene in multiple human cancers. However, its function in nasopharyngeal carcinoma (NPC) and underlying mechanism are still unclear. Materials and methods: We explored the expression of ANCR in NPC tissues and cells by real-time PCR and analyzed the relationship between ANCR expression and clinicopathological characteristics of NPC patients by Pearson’s chi-squared test. Then we inhibited ANCR expression in NPC cells using siRNAs and evaluated the effect of ANCR expression on cell proliferation, colony formation, and radiosensitivity by cell counting kit-8 assay and colony formation assay. We used RT-PCR and Western blot analyses to search target genes of ANCR. Also, we used RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation assay to study the molecular mechanism in this regulation. Results: We found that ANCR was upregulated in NPC tissues and cells. ANCR expression was significantly correlated with tumor size and TNM stage. Further, ANCR knockdown inhibited NPC cell growth and radiation resistance. Mechanistically, we found that PTEN was upregulated in ANCR knockdown NPC cells. In addition, RIP assay indicated that EZH2, the oncogenic histone methyltransferase of polycomb repressive complex 2, interacted with ANCR in NPC cells. More importantly, the binding of EZH2 and deposition of relevant negative histone marker H3K27me3 on PTEN promoter depended on ANCR expression. Conclusion: ANCR expression is upregulated in NPC and promotes NPC growth and radiation resistance through an epigenetic regulation of PTEN expression.

Background: Chronic rhinosinusitis with polyps (CRSwNP) is a global health concern. Nasal nitric oxide (nNO), a clinical biomarker, have been studied to assess the presence of airway mucosal inflammation. This study aimed to clarify the roles of nNO in diagnosis and endotypes of CRSwNP. Methods: Eighty-two CRSwNP patients and thirty healthy volunteers were recruited for this study. The patients were classified into eosinophilic CRSwNP (Eos CRSwNP) and non⁃eosinophilic CRSwNP (Non-Eos CRSwNP) endotypes by tissue eosinophil percentage. nNO levels were measured with an electrochemical sensor-based device. nNO levels and clinical factors were compared among the groups. Receiver-operating characteristic (ROC) curve and logistic regression analyses were performed to evaluate the predictive ability of the nNO for diagnosis and endotypes of CRSwNP. Results: Eos CRSwNP patients(143.9 ± 106.2, ppb) had lower nNO levels than Non-Eos CRSwNP(228.3 ± 109.2, ppb, p = 0.013) and healthy subjects(366.5 ± 88, ppb, p < 0.0001). Patients with atopy exhibited significantly higher levers of nNO compared with patients without atopy ( p < 0.05). For Eos CRSwNP diagnosis, nNO had high predictive value for Eos CRSwNP (AUC: 0.939; sensitivity: 76.74%; specificity: 96.67%; cut-off value: 231 ppb, p < 0.001). Furthermore, nNO levels were associated with CRSwNP endotypes (odds ratio: 1.010; 95% confidence interval: 1.003, 1.016%; p = 0.002). When the nNO concentration was 158 ppb, we could discriminate Eos CRSwNP from Non-Eos CRSwNP (AUC = 0.710, sensitivity: 76.92%; specificity, 60.47%, P = 0.001). After it was combinated by nNO, peripheral blood eosinophil count (PEAC) and VAS score, the AUC was increased to 0.894 (95%CI = 0.807 to 0.951, p < 0.0001, sensitivity:76.74%, specificity: 89.74%). Conclusions: nNO may have potential for non-invasive diagnosis and endotype of CRSwNP. nNO combined with PEAC and VAS score may be a good diagnostic tool for endotyps of Eos CRSwNP. However, the atopic status of the patients influenced the levels of nNO.

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.

This study aimed to investigate the role of miRNA-1225-5p (miR-1225) in laryngeal carcinoma (LC). We found that the expression of miR-1225 was suppressed in human LC samples, while CDC14B (cell division cycle 14B) expression was reinforced in comparison with surrounding normal tissues. We also demonstrated that enhanced expression of miR-1225 impaired the proliferation and survival of LC cells, and resulted in G1/S cell cycle arrest. In contrast, reduced expression of miR-1225 promoted cell survival. Moreover, miR-1225 resulted in G1/S cell cycle arrest and enhanced cell death. Further, miR-1225 targets CDC14B 3′-UTR and recovery of CDC14B expression counteracted the suppressive influence of miR-1225 on LC cells. Thus, these findings offer insight into the biological and molecular mechanisms behind the development of LC.

Traumatic tympanic membrane (TM) perforation is very common in clinical practice. Several biomaterials have been reported to play a role in TM reparation, whereas their functional recovery is limited when used alone. Meanwhile, the administration of biofactors could promote functional recovery, but rapid distribution and short half-time obstruct their application. To study the effect of traumatic TM regeneration, we prepared collagen membrane (CM) integrated with collagen-binding basic fibroblast growth factor (CBD-bFGF) and implanted into the injury site of perforated TM in Sprague-Dawley rats. The study on CBD-bFGF in vitro showed that CBD-bFGF accelerated the proliferation of human fibroblast cell HS-865 biologically and was released from CM gradually. In vivo study, through the gross anatomy, auditory brainstem responses assay, histological staining, and transmission electron microscopy observation at d7, d14, and d28 after the acute TM perforation, we found that CBD-bFGF-integrated CM promoted the healing rate at an early stage (∼7 days), reduced the healing time of perforated TM, and notably retrieved the structure and hearing of TM. These findings suggest that CM modified with CBD-bFGF could be therapeutically appropriate for the treatment of TM perforation.