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Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant cancers of the salivary gland, and 32.4-72.0% of SACC cases exhibit neural invasion (NI); however, the molecular mechanism underlying the high invasion potential of SACC remains unclear.The present study investigated the role of epidermal growth factor receptor (EGFR) in the AKT inhibition- or mitogen-activated protein kinase kinase (MEK)-induced NI and epithelialmesenchymal transition (EMT) in SACC cells using EGFR, PI3K, and MEK inhibitors. SACC-83 cell viability was assessed using an MTT assay, and a wound healing assay was performed to evaluate cell migration. Immunohistochemical staining with streptavidin peroxidase was used to detect the positive expression rate of EMT, AKT, phosphorylated (p)-AKT, ERK, and p-ERK proteins. The impact of EGFR, PI3K, and MEK inhibitors on tumor growth and NI was examined in a xenograft model in nude mice.EGF and EGFR are effective in increasing cell viability, migration, and invasion. SACC metastasis is affected by the PI3K/AKT and MEK/ERK pathways, both of which are initiated by EGF/EGFR. The EMT and NI are regulated by the EGF/EGFR, PI3K/AKT, and MEK/ERK pathways. The present findings demonstrate the importance of suppressed EGFR/AKT/MEK signaling in NI in SACC by neural-tumor co-culture in vitro. Furthermore, our preclinical experiment provides solid evidence that injection of EGFR, PI3K, and MEK inhibitors suppressed the tumor growth and NI of SACC cells in nude mice.It was identified that inhibitors of EGFR, PI3K/AKT or MEK/ERK suppressed the proliferation, migration, and NI of SACC-83 cells via downregulation of the PI3K/AKT or MEK/ERK pathways. It was also demonstrated that inhibition of EGFR abolishes EMT in SACC by inhibiting the signaling of PI3K/AKT and MEK/ERK. The present results suggest the potential effectiveness of targeting multiple oncogenes associated with downstream pathways of EGF/EGFR, as well as potential therapeutic targets to limit NI in SACC by PI3K/AKT or MEK/ERK inhibition.

Long non-coding RNAs (lncRNAs) have been shown to play pivotal roles in various types of human cancer, including oral squamous cell carcinoma (OSCC). However, the potential mechanisms of action of lncRNAs in OSCC remain to be fully elucidated. The aim of the present study was to further explore the potential mechanisms of action of lncRNAs in OSCC. We first analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly expressed lncRNAs which may be involved in the development of OSCC. Reverse transcription‑quantitative PCR (RT‑qPCR) was performed to analyze the expression levels of lncRNA H19. In addition, the correlation between H19 expression and the clinical characteristics and prognosis of patients with OSCC was statistically analyzed. The effects of H19 expression on OSCC cells were examined by using overexpression and RNA interference approaches in vitro and in vivo. To examine the competitive endogenous RNA (ceRNA) mechanisms, bioinformatics analysis and luciferase reporter assay were performed. In addition, the correlation between H19 and microRNA (miR)‑138 was detected. H19 was found to be upregulated in OSCC tissues and its high expression level was associated with the TNM stage and nodal invasion, and also correlated with a shorter overall survival of patients with OSCC. The knockdown of H19 significantly inhibited OSCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and induced apoptosis in vitro; it also suppressed subcutaneous tumor growth in vivo. In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR‑138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. On the whole, our findings suggest that H19 functions as an oncogene by inhibiting miR‑138 and facilitating EZH2 expression in OSCC. Thus, lncRNA H1 may represent a potential therapeutic target for OSCC.

Background and Purpose— Alterations of cerebral glucose metabolism are well anticipated during cerebral ischemia. However, detailed spatiotemporal characteristics of disturbed cerebral glucose metabolism during acute ischemia remain largely elusive. This study aims to delineate spatiotemporal distributions of [ 18 ]F-2-fluoro-2-deoxy- d -glucose (FDG) uptake using positron emission tomography imaging, particularly at the peri-ischemic zone, and its correlation with tissue outcome. Methods— The intraluminal suture middle cerebral artery occlusion model was used to induce focal cerebral ischemia in rats (n=48). All animals underwent sequential MRI and FDG positron emission tomography imaging at different times (30–150 minutes) after middle cerebral artery occlusion. MR and positron emission tomography images were coregistered. FDG uptake in the peri-ischemic zone was assessed in relation to middle cerebral artery occlusion duration, cerebral blood flow, apparent diffusion coefficient, and 24-hour T2 lesions. Results— Elevated FDG uptake was consistently observed at the peri-ischemic zone surrounding the presumed ischemic core with low FDG uptake. Both the spatial volume and the uptake level of the hyper-uptake region were inversely correlated with the duration of middle cerebral artery occlusion. The hyper-uptake regions exhibited a mild reduction of cerebral blood flow (28.2±3.2%) and apparent diffusion coefficient (9.1±1.4%) when compared with that in the contralateral hemisphere. Colocalization analysis revealed that, with reperfusion, an average of 12.1±1.7% of the hyper-uptake volume was recruited into final infarction. Conclusions— Elevated FDG uptake at the peri-ischemic zone is consistently observed during acute cerebral ischemia. The region with elevated FDG uptake likely reflects viable tissues that can be salvaged with reperfusion. Therefore, acute FDG positron emission tomography imaging might hold promise in the management of patients with acute stroke.