sincalide and Squamous-Cell-Carcinoma-of-Head-and-Neck

The purpose of the present study was to investigate the potentials of circ_0000311 in oral squamous cell carcinoma (OSCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for calculating the mRNA and miRNA level. Western blot was performed to determine protein expression. The binding sites between miR-876-5p and circ_0000311/Enhancer of zeste homolog-2 (EZH2) were predicted using bioinformatics tools and confirmed by luciferase and RNA pull-down assays. Cell proliferation was detected using CCK-8 and colony formation assay. Cell migration and invasion were detected using transwelll assay. Cellular functions were determined using CCK-8, colony, and transwell assay. The results showed that circ_0000311 was overexpressed in OSCC tissues and cells. However, circ_0000311 knockdown impeded the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells. Circ_0000311 targeted miR-876-5p, down-regulation of which promoted the aggressiveness of OSCC. Additionally, circ_0000311 sponged miR-876-5p to up-regulate a key regulator of EMT EZH2, which promoted the proliferation and aggressiveness of OSCC. Taken together, circ_0000311 aggravated the OSCC progression via regulating miR-876-5p/EZH2 axis.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Enhancer of Zeste Homolog 2 Protein; Head and Neck Neoplasms; Humans; MicroRNAs; Mouth Neoplasms; RNA, Circular; Sincalide; Squamous Cell Carcinoma of Head and Neck

The study was performed to ascertain the mechanism of sodium butyrate (NaB) mediating the proliferative and invasive properties of oral squamous cell carcinoma (OSCC) cells. The cell proliferative, migrating, and invasive potentials were detected by CCK-8, colony formation, EdU, and Transwell assays. The expression of proliferation- and invasion-related proteins, HDAC1, and HSPB7 in OSCC cells were evaluated by western blot. Immunofluorescence was also performed to evaluate the HDAC1 expression. The enrichment of histone deacetylase HDAC1 in the promoter region of HSPB7 was assessed by the ChIP assay. In vivo growth of OSCC cells was measured by tumorigenesis in nude mice (n=18). The t-test was employed for comparisons of data between the two groups. One-way ANOVA was utilized for comparisons of data among multiple groups, and repeated-measures ANOVA for comparisons of data at different time points among groups, followed by Bonferroni post-hoc test. The data showed that HDAC1 expression was highly upregulated in OSCC cells compared to human normal oral keratinocytes (HNOKs) (p<0.0001), and NaB diminished the HDAC1 expression in OSCC cells. NaB restricted OSCC cell proliferative, migrating, and invasive capabilities by downregulating HDAC1. HSPB7 expression was downregulated in OSCC cells versus HNOKs (p<0.0001). HDAC1 inversely orchestrated the HSPB7 expression in OSCC cells through histone deacetylation modification, and NaB augmented the HSPB7 expression by inhibiting HDAC1. Moreover, NaB inhibited OSCC cell growth in vivo by elevating HSPB7 levels through the HDAC1 repression. In conclusion, NaB restrained cell proliferation and invasion in OSCC cells via HSPB7 upregulation by decreasing the HDAC1 expression.

Topics: Animals; Butyric Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Histone Deacetylase 1; Histone Deacetylases; Histones; HSP27 Heat-Shock Proteins; Humans; Mice; Mice, Nude; MicroRNAs; Mouth Neoplasms; Sincalide; Squamous Cell Carcinoma of Head and Neck

The N. The cellular phenotypes of OSCC cells were determined by CCK-8 and transwell migration assays. The energy metabolism was detected using glucose uptake/lactate production assay and extracellular acidification rate analysis. The molecular interaction was tested by  RNA immunoprecipitation  assay.. Here, results indicated that IGF2BP2 was up-regulated in OSCC and that it acted as a predictor of poor prognosis. IGF2BP2 promoted the proliferation, migration and Warburg effect of OSCC cells in vitro. Mechanistical assays illustrated that IGF2BP2 directly interacted with HK2 mRNA by binding the 3'-UTR m

Topics: 3' Untranslated Regions; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glucose; Head and Neck Neoplasms; Humans; Lactates; MicroRNAs; Mouth Neoplasms; RNA-Binding Proteins; Sincalide; Squamous Cell Carcinoma of Head and Neck

Oral squamous cell carcinoma (OSCC) is characterized by high recurrence and metastasis and places a heavy burden on societies worldwide. Cancer cells thrive in a changing microenvironment by reprogramming lipidomic metabolic processes to provide nutrients and energy, activate oncogenic signaling pathways, and manage redox homeostasis to avoid lipotoxicity. The mechanism by which OSCC cells maintain lipid homeostasis during malignant progression is unclear.. The altered expression of fatty acid (FA) metabolism genes in OSCC, compared with that in normal tissues, and in OSCC patients with or without recurrence or metastasis were determined using public data from the TCGA and GEO databases. Immunohistochemistry was performed to examine the carboxylesterase 2 (CES2) protein level in our own cohort. CCK-8 and Transwell assays and an in vivo xenograft model were used to evaluate the biological functions of CES2. Mass spectrometry and RNA sequencing were performed to determine the lipidome and transcriptome alterations induced by CES2. Mitochondrial mass, mtDNA content, mitochondrial membrane potential, ROS levels, and oxygen consumption and apoptosis rates were evaluated to determine the effects of CES2 on mitochondrial function in OSCC.. We demonstrated that CES2 downregulation plays an important role in OSCC by maintaining lipid homeostasis and reducing lipotoxicity during tumor progression and may provide a potential therapeutic target for OSCC.

Topics: Carboxylesterase; Carboxylic Ester Hydrolases; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Diglycerides; DNA, Mitochondrial; Fatty Acids, Nonesterified; Head and Neck Neoplasms; Homeostasis; Humans; Mitochondria; Mouth Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Reactive Oxygen Species; Signal Transduction; Sincalide; Squamous Cell Carcinoma of Head and Neck

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors, and the main cause of death is metastasis. Overexpression of aurora kinase A (AURKA) plays an important role in the metastasis of LSCC. However, the mechanism by which AURKA promotes the metastasis of LSCC is poorly understood. Recent accumulating evidence indicates that epithelial-mesenchymal transition (EMT) may be one of the mechanisms of tumor metastasis. In the present study, we studied whether AURKA may induce EMT to promote the metastasis of LSCC. CCK-8 and plate colony-formation assays were carried out to show that AURKA significantly promoted the proliferation of Hep2 cells. Immunofluorescence staining and western blotting showed that EMT-related proteins changed in a time-dependent manner along with the alteration of AURKA, with decreased expression of N-cadherin, vimentin and slug and increased expression of E-cadherin. Additionally, downregulation of the expression of AURKA inhibited FAK/PI3K pathway activity. Inhibition of the FAK/PI3K pathway caused less mesenchymal-like characteristics and reduced the mobility, migration and invasion of Hep2 cells. In conclusion, AURKA may induce EMT to promote metastasis via activation of the FAK/PI3K pathway in LSCC. Those regulatory factors may present new diagnostic biomarkers and potential therapeutic targets for LSCC.

Topics: Aurora Kinase A; Cadherins; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Epithelial-Mesenchymal Transition; Focal Adhesion Kinase 1; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Lymphatic Metastasis; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases; Signal Transduction; Sincalide; Snail Family Transcription Factors; Squamous Cell Carcinoma of Head and Neck; Vimentin