Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.

Yin Yang 1 (YY1) is a key transcription factor that exerts functional roles in the cell biological process of various cancers. The current study aimed to elucidate the role and mechanism of YY1 in laryngeal squamous cell carcinoma (LSCC). YY1 mRNA and protein expression in human LSCC cell lines was detected by RT-qPCR and Western blot analysis. An interaction of YY1, GAS5, and p53 protein stability was predicted and confirmed by bioinformatics, ChIP, Co-IP, RIP, and FISH assays. Following loss- and gain-function assays, LSCC cell proliferation, colony formation, cell cycle, telomere length and telomerase activity were evaluated by CCK-8 assay, colony formation assay, flow cytometry, and PCR-ELISA, respectively. Nude mice were xenografted with the tumor in vivo. LSCC cell lines presented with upregulated expression of YY1, downregulated GAS5 expression, and decreased p53 stability. YY1 inhibited the expression of GAS5, which in turn recruited p300 and bound to p53, thus stabilizing it. Moreover, YY1 could directly interact with p300 and suppressp53 stability, leading to enhancement of cell proliferation, telomere length and telomerase activity in vitro along with tumor growth in vivo. Collectively, YY1 can stimulate proliferation and telomerase activity of LSCC cells through suppression of GAS5-dependent p53 stabilization or by decreasing p53 stability via a direct interaction with p300, suggesting that YY1 presents a therapeutic target as a potential oncogene in LSCC development and progression.

Introduction: The aim of the study was to investigate how adipose-derived mesenchymal stem cells regulate the balance between regulatory T (Treg) cells and Th17 cells through the IL-2/JAK-3/STAT-5 signaling pathway in a rat model of allergic rhinitis (AR). Methods: Adipose-derived stem cells (ADSCs) were used to treat an ovalbumin (OVA)-induced AR rat model. The pathological changes and nasal symptoms were observed by HE staining and scanning electron microscopy. The concentrations of OVA-sIgE, IL-10, and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of JAK-3, STAT-5, forkhead box P3 (Foxp3), and retinoic acid-associated orphan receptor γt (RORγt) in nasal mucosa were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of IL-2, JAK-3, and STAT-5 proteins in nasal mucosa was detected by Western blotting, and the expression patterns of these proteins were analyzed. Results: ADSCs significantly reduced nasal symptoms and histological abnormalities by significantly reducing the levels of OVA-sIgE, IL-17 and increasing IL-10 levels. The expressions of IL-2, JAK-3, STAT-5, Foxp3, and RORγt in the nasal mucosa of AR rats were abnormal, but ADSCs treatment significantly restored this change. Conclusion: ADSC can control the development of Treg/Th17 cells by the IL-2/JAK-3/STAT-5 signaling pathway and reduce OVA-induced allergic inflammation.

Head and neck cancer (HNC) is a common disease in otorhinolaryngology. Its prevalence is higher in men than in women and is mostly related to tobacco, alcohol and viral infections. Despite significant advances in the treatment of HNC in recent years, the mortality rate is still high and most patients are diagnosed at an advanced stage, and the prognosis for these patients is even worse. Earlier metastasis makes the treatment of HNC trickier. Therefore, actively seeking ways to treat HNC more effectively has been the goal of head and neck surgeons. Potassium (K⁺) channels are the most diverse ion channels found in all areas of life. Voltage-gated potassium (Kv) channels are the most important subfamily of K⁺ channels. Multiple Kv channels are associated with the development of HNC. This review focuses on several Kv channels associated with HNC.

Head and neck cancer (HNC) is a common malignant disease in otorhinolaryngology; however, its pathogenesis remains to be fully elucidated. Currently, the treatment for HNC mainly comprises surgery assisted by other methods, including radiotherapy, chemotherapy and immunotherapy. After surgical treatment, the laryngeal function, and swallowing and breathing abilities of patients can be affected to a certain extent, and the loss of vocal ability can cause daily communication obstacles and affect the physical and mental health of patients. HNC recurrence makes retreatment challenging. Ferroptosis is a type of iron‑dependent regulated cell death caused by plasma membrane rupture and lipid peroxidation, and its occurrence is related to HNC. The present review aimed to describe the organelles that influence ferroptosis, the factors that activate and inhibit ferroptosis, and the role of ferroptosis in the pathogenesis, treatment and prognosis of HNC.

Background: Laryngeal cancer (LC) is characterized by high mortality and remains challenging in prognostic evaluation and treatment benefits. Ubiquitin-related genes (UbRGs) are widely involved in cancer initiation and progression, but their potential value in LC is unknown.Methods: RNA-seq and clinical data of LC were obtained from TCGA and GEO. UbRGs that independently influenced the overall survival (OS) of LC patients were screened with differential expression, COX and LASSO regression analyses. A prognostic signature was then established and assessed for its predictive value, stability and applicability using Kaplan-Meier analysis and receiver operating characteristic curves. The nomogram was further generated in combination with the signature and clinical characteristics. Characterization of immune properties and prediction of drug sensitivity were investigated on the signature-based subgroups using a panel of in silico platforms. Verification of gene expression was conducted with Western blot, qRT-PCR and ELISA, ultimately.Results: PPARG, LCK and LHX1 were identified and employed to construct the UbRGs-based prognostic signature, showing a strong ability to discriminate LC patients with distinct OS in TCGA-LC and GSE65858, and excellent applicability in most clinical conditions. The nomogram showed higher predictive value and net clinical benefit than traditional indicators. As evaluated, the low-risk group had a more activated immune function, higher infiltration of anti-cancer immune cells and stronger expression of immune-promoting cytokines than the high-risk group. Immune properties were also correlated with individual signature genes. PPARG and LHX1 were negatively correlated, whereas LCK positively correlated, with the immuno-promoting microenvironment. Additionally, chemotherapy would be more effective in high-risk patients, while immune checkpoint inhibitors would be more effective in low-risk patients. Finally, dysregulation of the signature genes was confirmed in LC cell lines by Western blot, and PPARG knockdown significantly reduced the expression of the immunosuppressive cytokines IL6, TGFB1, TGFB2 and VEGFC by qRT-PCR and ELISA.Conclusion: We have developed a UbRGs-based signature for LC prognostic evaluation that is valuable in clinical application, indicative of the immune microenvironment and beneficial for individualized treatment guidance.