To elucidate the genetic effect involved in the premalignant progression of chronic inflammation to cancer, we performed microRNA and mRNA profiling in oral lichen planus (OLP), oral squamous cell carcinoma (OSCC), and normal tissue from the same patients. We demonstrate the involvement of a suppressive microRNA, miR-375, in the regulation of this premalignant progression via KLF5, a transcription factor that modulates the expression of genes contributing to proliferation and apoptosis. We found that miR-375 abundance decreased in tissues with progression from the normal state to OLP and subsequently to OSCC. Restoration of miR-375 by transduction of a synthetic mimic into OSCC cells repressed cellular proliferation and promoted apoptosis, with concomitant down-regulation of KLF5, and vice versa. The direct binding of miR-375 to the 3′-untranslated region of KLF5 was further confirmed. Additionally, Survivin (BIRC5), a target of KLF5, was also regulated by miR-375, explaining the susceptibility of miR-375-mimic transfected cells to apoptosis. Further analysis of clinical specimens suggested that expression of KLF5 and BIRC5 is up-regulated during the progression from inflammation to cancer. Our findings provide novel insights into the involvement of microRNAs in progression of inflammation to carcinoma and suggest a potential early-stage biomarker or therapy target for oral carcinoma.

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Benign parotid tumor is one of the most common neoplasms in head and neck region. Its therapeutic methods have been debatable topics over the past 100 years. Recently, some surgeons suggest that extracapsular dissection (ECD) instead of superficial parotidectomy (SP) for treatment of benign parotid tumor. This study aimed to compare ECD with SP in the treatment of benign parotid tumors by a meta-analysis.We searched Cochrane Library, PubMed, Embase, Ovid, and Web of Science databases on February 14, 2015 for studies that assessed clinical outcomes of SP and ECD as surgical techniques for the management of benign parotid tumors. Outcome data were evaluated by pooled risk ratio (RR) and corresponding 95% confidence interval (CI).After serious scrutiny, a total of 14 cohort studies with 3194 patients were included in this meta-analysis. The pooled RR revealed that there were no significant difference in tumor recurrence rate between ECD and SP (fixed-effect model: RR = 0.71, 95% CI = 0.40–1.27, P = 0.249; random-effect model: RR = 0.67, 95% CI = 0.38–1.23, P = 0.197). However, there were significantly lower incidences of transient facial nerve dysfunction (FND), permanent FND, and Frey's syndrome in patients of ECD group compared with SP group.ECD might be a good choice in treatment of the benign parotid tumor that were mobile, small, located in superficial lobe and without adhesion to facial nerve; ECD should be performed by the experienced surgeons with ability of dissection facial nerve, who should perform SP if tumor is found adhere to facial nerve during an operation; and a multicenter randomized control trial study is necessary to decide the optimal treatment of benign parotid tumor.

Botulinum toxin A (BTXA) has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor (M3 receptor) and aquaporin-5 (AQP5) mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular glands.

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Intraglandular injection of botulinum toxin type A (BoNT/A) is an effective treatment for sialorrhea. Despite numerous experimental and clinical studies on inhibition of saliva section by BoNT/A, the proteolysis of synaptosomal-associated protein 25 (SNAP-25) following BoNT/A treatment has not yet been confirmed in the salivary gland after injection of BoNT/A. More important, it is not known whether BoNT/A exerts a direct effect in acinar cells. Here, we show that injection of BoNT/A into the rat submandibular gland (SMG) decreased salivary flow in a dose-dependent manner; the inhibitory effect lasted at least 4 wk, and salivary flow recovered to normal levels by 12 wk. During the inhibitory period, SMG neurons and synapses expressed lower levels of full-length SNAP-25, and cleavage of SNAP-25 was observed, as indicated by detection of reduced molecular weight SNAP-25 using Western blotting. In addition, the water channel aquaporin 5 (AQP5) was downregulated and abnormally distributed in rat SMG after injection of BoNT/A. The direct effects of BoNT/A on AQP5 expression and distribution were assessed in vitro to exclude the influence of BoNT/A-induced inhibitory neurotransmission. In stable GFP-AQP5-transfected SMG-C6 cells, treatment with BoNT/A reduced the cell surface protein level of AQP5 in a dose- and time-dependent manner without affecting total AQP5 protein expression. Cell surface biotinylation and immunofluorescence demonstrated translocation of AQP5 from the membrane to the cytoplasm, which was confirmed by decreased levels of AQP5 protein in the membrane fraction and increased levels in the cytoplasmic fraction, suggestive of AQP5 redistribution. Taken together, these results indicated that BoNT/A reversibly decreased saliva secretion in rat SMGs through not only the presynaptic SNAP-25 cleavage but also the postsynaptic AQP5 redistribution. These data provide the first evidence for a direct effect of BoNT/A on the salivary gland.