LAUSR

Our microRNA (miRNA) expression signatures of oral squamous cell carcinoma (OSCC) revealed that miR-450a was significantly increased in cancer tissues compared with normal epithelium. In this study, we focused on the functional significance of miR-450a in cancer cells and identification of miR-450a-regulated novel targets in OSCC. Overexpression of miR-450a in DOK and SAS cells showed significant inhibition of cell adhesion and induction of cell invasiveness, suggesting that miR-450a functions as an onco-miRNA. We performed genome-wide gene expression analysis to search for miR-450a-regulated molecular targets. Gene expression data and luciferase reporter assays revealed that TMEM182 was directly targeted by miR-450a. The miR-450a-reduced cellular adhesion was blocked by TMEM182 restoration, suggesting that miR-450a exhibits its oncogenic activity through negatively regulating TMEM182 level. Furthermore, miR-450a expression could be induced by the cytokine TNF-α primarily through activating extracellular signal-regulated kinase (ERK) signaling pathway. ERK inhibitor prevented the TNF-α-induced miR-450a expression and enhanced adhesion ability. Taken together, these data indicate that TNF-α/ERK-dependent expression of miR-450a plays an important role in mediating cellular adhesion and invasiveness, and scavenging miR-450a function using antagomir may have therapeutic potential for the treatment of OSCC. (The study was supported by the following grants: MOST 103-2320-B-006-036-MY3 and MOST 105-2325-B-400-001 from the Ministry of Science and Technology of Taiwan, ROC) Citation Format: En-Wei Hsing, Shine-Gwo Shiah, Ching-Chuan Kuo, Jang-Yang Chang. miRNA-450a suppresses adhesion but promotes invasion through targeting of TMEM182 in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2017-1475