CYP4F12 is a potential biomarker and inhibits cell migration of head and neck squamous cell carcinoma via EMT pathway.

Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor of head and neck. Due to the insidious nature of HNSC and the lack of effective early diagnostic indicators, the development of novel biomarkers to improve patient prognosis is particularly urgent. In this study, we explored and validated the correlation between cytochrome P450 family 4 subfamily F member 12 (CYP4F12) expression levels and HNSC progression using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets and collected patient samples. We analyzed the association of CYP4F12 expression with clinicopathological features, immune correlation and prognosis. Finally, we analyzed the correlation between CYP4F12 and pathways, and verified by experiments. The results showed that CYP4F12 was low expressed in tumor tissues, participated in a variety of phenotypic changes of HNSC and affected immune cell infiltration. Pathway analysis indicated that CYP4F12 may play a key role in tumor cell migration and apoptosis. Experimental results showed that over-expression of CYP4F12 inhibited cell migration and enhanced the adhesion between cells and matrix by inhibiting epithelial-mesenchymal transition (EMT) pathway in HNSC cells. In conclusion, our study provided insights into the role of CYP4F12 in HNSC and revealed that CYP4F12 may be a potential therapeutic target for HNSC.

Comprehensive analysis reveals CCDC60 as a potential biomarker correlated with prognosis and immune infiltration of head and neck squamous cell carcinoma.

Background: Coiled-coil domain containing 60 (CCDC60) is a member of the CCDC family, which participates in the progression of many types of cancer. However, the prognostic value of CCDC60 in head and neck squamous cell carcinoma (HNSC) and its function in tumor immunity remain unclear. Methods: CCDC60 expression and its prognostic potential in HNSC were evaluated by bioinformatics approaches, which was validated in human HNSC samples. Genetic alteration analysis of CCDC60 and the underlying biological function of CCDC60 related co-expressed genes in HNSC were analyzed. The impact of CCDC60 on the regulation of immune infiltration in HNSC was comprehensively investigated. In vitro, a series of functional assays on CCDC60 were performed in HNSC cells. Results: Our study has indicated that compared with the adjacent normal tissues, CCDC60 expression was considerably downregulated in HNSC tissues. High CCDC60 expression was connected with favorable outcome of HNSC patients, and its prognostic significance was examined by distinct clinical characteristics. We identified the CCDC60-related co-expression genes, which were mainly enriched in the NOD-like receptor signaling pathway associated with the inhibition of tumor growth, leading to a better prognosis of HNSC patients. In vitro, CCDC60 overexpression significantly inhibited the growth, migration and invasiveness but regulated cell cycle progression, and promoted cell adhesion of Fadu and Cal27 cells. Additionally, high CCDC60 expression had strong connections with the infiltrating levels of immune cells, immune marker sets, immunomodulators and chemokines in HNSC, suggesting that targeting CCDC60 could be a promising strategy to enhance the efficacy of immunotherapy for HNSC patients. Conclusion: Tumor suppressor CCDC60 may be identified as a prognostic and immune-related indicator in HNSC, which had the potential functions in regulating the immune infiltration of HNSC and improving the response to immunotherapy for HNSC patients.

TIPE2 Inhibits Migration and Promotes Apoptosis as a Tumor Suppressor in Hypopharyngeal Carcinoma.

BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) is a common malignant cancer characterized by high metastasis and infiltration. The development of new approaches for the early diagnosis and identification of new therapeutic targets is essential. TIPE2 is well known as a tumor suppressor and related to a favorable prognosis of HSCC. However, its underlying mechanism remains unclear. METHODS AND MATERIALS: TIPE2 expression was determined by immunohistochemistry and RT-qPCR. A TIPE2 overexpression stable cell line was generated by lentivirus infection. TIPE2 and other related protein levels were detected by western blotting. The cell cycle and apoptosis were performed by flow cytometric analysis. Cell proliferation was measured with a Cell Counting Kit-8 (CCK-8) assay, and the activity of caspase-3 and caspase-7 was assessed by Caspase-Glo® 3/7 Assay. All data were analyzed with SPSS 25 and GraphPad Prism 8.0. RESULTS: TIPE2 expression was significantly down-regulated in HSCC. Low TIPE2 expression may be associated with poor prognosis in HSCC. TIPE2 overexpression markedly inhibited tumor cell migration. Moreover, TIPE2 decreased cell proliferation but promoted apoptosis. TIPE2 suppressed tumor growth by activating Epithelial-Mesenchymal Transition (EMT) and the extrinsic apoptosis pathway. CONCLUSION: TIPE2 inhibited tumor progression by suppressing cell migration but promoting apoptosis. TIPE2 can be a new therapeutic target in HSCC.

Comparison of treatment modalities for selected advanced laryngeal squamous cell carcinoma.

PURPOSE: The authors aimed to clarify the optimal treatment strategy and the indication of different treatments in managing advanced laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 9700 patients with advanced (T3-4aN0-3M0) LSCC who treated with (1) surgery alone, (2) surgery plus adjuvant radiation with or without chemotherapy (aCRT/RT), or (3) definitive CRT/RT was retrieved from the SEER database. The propensity score matching (PSM) was applied to balance confounding factors. Kaplan-Meier method and Cox proportional hazards regression were used to comparing the overall survival (OS) of patients. RESULTS: After optimal matching, 907 patients were screened from each treatment cohort. Kaplan-Meier and multivariate analyses presented that patients treated with surgery plus aCRT/CT had significantly longer OS than those treated with either surgery alone or CRT/RT, even after PSM. However, significant interactions were tested in treatment effects in stratified analyses of the primary subsite, T stage, N stage, and insurance status (PInteraction < 0.05 for all). Specifically, surgery plus aCRT/CT significantly improved the OS of patients with supraglottic, T4a, and N + tumors (P < 0.001 for all), while three treatment modalities achieved equal OS rates for patients with glottic, T3, and N0 tumors (P > 0.05 for all). Besides, supraglottic tumors presented a poorer prognosis than glottic subsite. CONCLUSION: Current study suggests that surgery with aCRT/RT is the preferred initial therapy for patients with T4a tumors, whereas patients with T3 tumors could be treated with either surgery (followed by aCRT/RT if it presents N +) or definitive CRT/RT for achieving laryngeal preservation. More-intense treatment should be emphasized for advanced supraglottic cancer.

Nootkatone protects cartilage against degeneration in mice by inhibiting NF-κB signaling pathway.

Osteoarthritis is a common chronic disease associated with chondrocyte inflammation and cartilage matrix hydrolyzation. Studies report that IL-1ß plays a critical role in osteoarthritis. Anti-inflammatory effect of nootkatone has been explored in acute and chronic inflammatory disease, thus the current study sought to explore its therapeutic effect in osteoarthritis. Notably, the effect of nootkatone in osteoarthritis has not been elucidated. Therefore, murine primary chondrocytes were extracted and ACLT induced OA mouse model was established in the current study to explore the therapeutic effect of nootkatone in OA both in vitro and in vivo. The findings showed that nootkatone inhibited inflammatory response and protected cartilage balance in murine primary chondrocyte. Further analysis showed that nootkatone suppressed inflammation and protected cartilage against degeneration induced by ACLT surgery in mice. The cellular mechanism of the protective effect of nootkatone in osteoarthritis and associated signaling pathway was identified as the NF-κB signaling pathway. In summary, the findings of the current study indicated that nootkatone is a potential therapeutic agent for OA.

GPR12 inhibits migration and promotes apoptosis in esophageal cancer and hypopharyngeal cancer cells.

BACKGROUND: G protein-coupled receptor 12 (GPR12) is an orphan receptor with no confirmed endogenous ligands. It plays important roles in both physiological and pathological conditions such as neurogenesis and neural inflammation. However, it remains unclear whether GPR12 regulates carcinogenesis and progression in head and neck squamous cell carcinoma (HNSCC), such as esophageal cancer (EC) and hypopharyngeal cancer (HC). METHODS: The Cancer Genome Atlas (TCGA) database was applied to explore the expression of GPR12. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of GPR12 in cancer tissues. Wound healing and transwell assays were carried out to verify the effect of GPR12 on cell migration. Flow cytometric analysis and caspase-Glo 3/7 assay were carried out to verify the influence of GPR12 on cell apoptosis. Western blotting was used to measure the expression of proteins related to migration and apoptosis. RESULT: The qRT-PCR analyses showed that the expression of GPR12 decreased in EC and HC than that in their paired adjacent normal tissues. Wound healing assay and transwell assay demonstrated that GPR12 inhibited tumor cell migration. Flow cytometry analysis and Caspase-Glo 3/7 Assay suggested that GPR12 promoted apoptosis. The mechanism of GPR12 may function via modulating caspase-7, E-cadherin, and α-catenin in EC and HC cells. CONCLUSION: In conclusion, GPR12 induced apoptosis by activating caspase-7 and inhibited migration through epithelial-to-mesenchymal transition (EMT) in EC and HC. Our findings demonstrated that GPR12 as a potential tumor suppressor mediated cell migration and apoptosis in EC and HC.

Glycitin Suppresses Cartilage Destruction of Osteoarthritis in Mice.

Osteoarthritis (OA), a chronic joint disease, is characterized by cartilage surface erosion, subchondral bone rebuilding, and formation of osteophytes. To date, the nosogenesis and underlying mechanisms of OA have not yet been elucidated. However, it is widely accepted that TNF-α is a crucial cytokine in the development of OA. Glycitin, a natural isoflavone extracted from legumes, affects physiological reactions and pathological responses. Recently, the anti-inflammatory effect of glycitin has been reported. However, the function of glycitin in cartilage degeneration in OA remains to be investigated. In the current study, primary murine chondrocytes were isolated and stimulated by TNF-α to evaluate the anti-inflammatory effects and protective function of glycitin in chondrocytes. In vivo, the ACLT mouse model, a frequently-used OA model, was used to further examine the therapeutic role of glycitin in cartilage degeneration and inflammation in OA. Consequently, glycitin functions were examined both in vivo and in vitro. Moreover, the underlying mechanism of action of glycitin was investigated and was found to involve the NF-κB signaling pathway. Collectively, this study suggests that glycitin can be potentially used for the treatment of joint degenerative diseases, including OA.