Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor survival and is the sixth most common cancer worldwide. Gastroesophageal reflux is a common event in SCCHN patients. GPR4 is a proton-sensing G-protein coupled receptor, which can be activated by acidosis. The objective of this study was to explore the role of GPR4 in acid exposure and tumor angiogenesis in SCCHN. In this study, we confirmed that overexpressing GPR4 in SCCHN cells could increase the expression and secretion of IL6, IL8 and VEGFA at pH 5.9. This effect could be inhibited by SB203580 (a p38 inhibitor). Western blot analysis indicated that phosphorylation of p38 increased in GPR4 infected cells at pH 5.9, which could be inhibited by SB203580. In tube formation assay, HMEC-1 cells were incubated with conditioned medium (CM, pH 5.9, 6.5, 7.4) derived from control and GPR4 infected SCCHN cells. Tube length was significantly increased in HMEC-1 cells incubated with CM from GPR4 infected cells compared with control cells at pH5.9, which indicated the pro-angiogenic effect of GPR4 in acidic pH. The neutralizing antibodies of IL6, IL8 and VEGFA could inhibit tube formation of HMEC-1 cells. In vivo, the effect of GPR4 on angiogenesis was investigated with the chick chorioallantoic membrane (CAM) model. Control and GPR4 infected SCCHN cells were seeded onto the upper CAM surface (n = 5 in each group) and 5 μL DMEM/F12 (pH 5.9, 6.5, 7.4) was added to the surface of the cell every 24 h. Four days later, the upper CAM were harvested and the ratio of the vascular area to the CAM area was quantified using Image-Pro Plus 6.0 software. GPR4 infected cells could recruit more vascular than control cells at pH5.9. In conclusion, we suggested that GPR4 induces angiogenesis via GPR4-induced p38-mediated IL6, IL8 and VEGFA secretion at acidic extracellular pH in SCCHN.
Objective: This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC). Methods: The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. Results: There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC. Conclusion: This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.
Rationale: Spindle cell lipoma is a rare, uncommon type of benign lipomatous tumor, a distinct group of lipomas composed of mature adipocytes, uniform spindle cells, and multinucleated giant cells associated with ropey collagen. Immunohistochemically, spindle cell lipoma is characterized by the diffuse expression of CD34. Patient concerns: We present a rare case of a 56-year-old man who complained of vomiting out of a smooth and giant mass in the oral cavity provoked by an intra-abdominal pressure increase. Oral examination revealed an elongated mass protruding from the mouth. Computed tomography of the patient showed a mass from left pyriform to oral cavity, with 2.38 × 2.78 × 16.86 cm in size. The flexible fiberscope showed that the pedicle of the elongated mass originated from the posterior wall of the hypopharynx, corresponding to the left pyriform fossa. Diagnosis: Histopathologically, the tumor was mainly composed of hyperplastic adipocytes, admixed with small blood vessels, and scattered inside adipose tissue spindle cells. The immunohistochemical profile revealed positivity of spindle cells for CD34, negativity for S100, and low proliferation with Ki67, which confirmed the diagnosis of spindle cell lipoma and revealed its benign behavior. Interventions: The patient underwent hypopharyngeal mass resection using transoral suspension laryngoscopy. Outcomes: No recurrence was found after 5 months of follow-up. Lessons: Spindle cell lipoma is difficult to diagnose early because of slow growth and subtle symptomatology. This entity should be differentiated from several benign or malignant subtypes of lipomas, including liposarcomas. In this case, the spindle cell lipoma is large and originates from the hypopharynx, which is a rare entity and presents with atypical symptoms. This case gave rise to further studies on the clinical and pathologic characteristics of this tumor in the future.
Background: Radiotherapy greatly benefits patients with tumors, but not all patients show favorable treatment response. This study investigated the impact of forkhead box protein C2 (FOXC2)-mediated a disintegrin and metalloprotease 12 (ADAM12) on the radiosensitivity of head and neck squamous cell carcinoma (HNSCC).Methods: After transfection and ionizing radiation, the biological activities of HNSCC cells were assessed. The relationship between ADAM12 and FOXC2 was verified. A xenograft model was used to evaluate the effect of FOXC2 knockdown on HNSCC growth in the context of radiation therapy.Results: FOXC2 and ADAM12 were upregulated in irradiated CAL-27 and HN4 cells. Knockdown of FOXC2 suppressed the malignant behaviors of CAL-27 and HN4 cells and inhibited the growth of transplanted tumors in nude mice. FOXC2 could bind ADAM12 promoter. Overexpression of ADAM12 reversed the promotion of FOXC2 silencing on the radiosensitivity of HNSCC cells.Conclusions: FOXC2 regulates the radiosensitivity of HNSCC by targeting ADAM12.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.