J Cancer 2019; 10(12):2720-2734. doi:10.7150/jca.31825

Research Paper

Dysregulation of MiR-519d Affects Oral Squamous Cell Carcinoma Invasion and Metastasis by Targeting MMP3

Yu Jin1,2, Yuexiu Li3, Xin Wang1,2, Ya Yang1,2,✉

1. Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.
2. Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, 200000, PR China.
3. Department of Stomatology, Tai'an Central Hospital, Tai'an, Shandong 271000, P.R. China.

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Citation:
Jin Y, Li Y, Wang X, Yang Y. Dysregulation of MiR-519d Affects Oral Squamous Cell Carcinoma Invasion and Metastasis by Targeting MMP3. J Cancer 2019; 10(12):2720-2734. doi:10.7150/jca.31825. Available from http://www.jcancer.org/v10p2720.htm

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Abstract

MicroRNA-519d (miR-519d) has been reported to play important roles in tumor development and progression in multiple cancers, either as tumor suppressor or tumor promotor. However, the expression level, biological function and molecular mechanisms of miR-519d in oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aims of this study were to investigate the functional role of miR-519d in OSCC and the possible underlying regulatory mechanism. In this study, we found that miR-519d was significantly downregulated in OSCC tissues and cell lines compared with normal oral mucosae and normal oral epithelial cells. Importantly, downregulation of miR-519d was closely correlated with the lymph node metastasis, advanced tumor stage and poor overall survival of OSCC patients. Furthermore, miR-519d significantly inhibited the migration and invasion of OSCC cells. Using bioinformatics and biological approaches, we showed that miR-519d directly targeted matrix metalloproteinase-3 (MMP3), which might account for the underlying mechanism involved in the miR-519d mediated suppression of OSCC progression. What is more, miR‐519d expression was inversely correlated with MMP3 expression in OSCC tissues, and high levels of MMP3 expression in OSCC tissues were also associated with the metastasis and poor prognosis of these patients. In addition, we further identified that miR-519d acted as a regulator of epithelial-mesenchymal transition (EMT) in OSCC cells. Overall, the present study highlighted miR-519d as a tumor suppressor in OSCC by targeting MMP3 and supported biological and clinical links between miR-519d-MMP3 and OSCC, thus indicating the potential therapeutic value of miR-519d for alleviating OSCC metastasis.

Keywords: miR-519d, oral squamous cell carcinoma, invasion, metastasis, MMP3, epithelial-mesenchymal transition (EMT)