br Conclusion br Conflict of interest br Introduction Oral

Conclusion
Conflict of interest
Introduction Oral cancer may originate from lips, lower and upper alveolar ridges, hard palate, sublingual region, buccal mucosa, anterior two-thirds of the tongue as well as retromolar trigone and floor of the mouth (World Health Organization, 2013). As the most common histological type of oral cancer, oral squamous cell carcinoma accounts for more than 95 % of all cases (Ayaz, Saleem, Azim, & Shaik, 2011). In spite of the efforts that have been made on the treatment and prevention of oral squamous cell carcinoma, this disease is still one of the leading causes of cancer-related death, which is responsible for more than 145,000 deaths worldwide every year (Markopoulos, 2012). In some developing counties such as India, oral squamous cell carcinoma now is the number 1 killer of human lives (Ferlay et al., 2015). In recent years, incidence of oral squamous cell carcinoma shows an increasing trend, especially in young population, the increased incidence of this disease caused high mortality rate in young age (Patel et al., 2011). Currently, surgical resection is still the only radical treatment for most malignancies including oral squamous cell carcinoma, while most patients lost the best timing for surgical operations by the time of diagnosis due to the lack of classic symptoms in the early stages. Therefore, how to improve early diagnosis and treatment is a main task for the treatment of oral squamous cell carcinoma. MicroRNA, or miRNA, is group of RNA molecule of about 22 nucleotides without protein-coding function. MicroRNAs are widely distributed in plants, animals and even some viruses and participant in both normal physiological and pathological processes by post-transcriptional regulation of gene expression and RNA silencing (Bartel, 2004). Participation of miRNAs has been observed in nearly all aspects of the onset, development and progression of oral squamous cell carcinoma (Manikandan et al., 2016). MiR-200c plays a role as tumor suppressor gene in several types of malignancies (Li et al., 2014; Shimono et al., 2009). It has been reported that miR-200c inhibits both tumor growth and metastasis presumptive head and neck squamous cell carcinoma stem diltiazem hydrochloride (Lo et al., 2011), and the functions of miR-200c in endometrial carcinoma is likely achieved through the inactivation of Akt pathway by targeting BMI-1 (Li et al., 2007). However, to date, the involvement of miR-200c, and the molecular mechanism of its action in oral squamous cell carcinoma still hasn’t been reported.
Materials and methods
Results
Discussion In spite of the complexity of the pathogenesis of oral squamous cell carcinoma, involvement of miRNAs in the molecular mechanism of this disease has been widely studied. miRNA-155 is highly expressed in cancer nest, vascular endothelium and inflammatory area, and the abnormally upregulated miRNA-155 is closely correlated with the poor prognosis (Shi et al., 2015). In contrast, miR-433 was downregulated in patients with oral squamous cell carcinoma compared with normal healthy people, indicating its possible role as a tumor suppressor gene in this disease (Wang et al., 2015). The functionality of miR-200c has been studied in several human diseases, including different types of malignancies, such as non-small cell lung cancer (Li et al., 2014) and breast cancer (Shimono et al., 2009). Downregulation of miR-200c, which is common during tumor development, not only promotes tumor growth and progression but also causes adverse prognosis (Wilczynski et al., 2018). In our study, significantly increased expression level of miR-200c in tumor tissues comparing with adjacent healthy tissues was observed from about 89.7 % of patients with oral squamous cell carcinoma. In addition, expression level of miR-200c in serum was significantly lower in patients with oral squamous cell carcinoma than that in healthy controls, and was further decreased with the increased stage of primary tumor. Those data suggest that downregulation of miR-200c is very likely to be involved in the pathogenesis of oral squamous cell carcinoma. Diagnosis and treatment of oral squamous cell carcinoma is still challenged by the lack of effective and reliable diagnostic and prognostic markers. Our study showed that miR-200c could be used to effectively distinguish oral squamous cell carcinoma patients from healthy controls, and low serum miR-200c level predicted poor survival. It’s worth to mention that miR-200c was abnormally expressed in several malignancies (Li et al., 2014; Shimono et al., 2009), which may affect the specificity of miR-200c in the diagnosis and prognosis of oral squamous cell carcinoma. Therefore, combination of multiple biomarkers is needed.