Inhibitory effect of the Notch pathway-inhibitor DAPT on invasion and metastasis of tongue cancer via lncRNA-KAT14 regulation

F. Liu, H.-X. Chu, J.-S. Han, X. Sun, J. Chen, X.-L. Qiu, X.-H. Zheng, B. Jia, J.-J. Zhao

Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, China. jianjiangzhao123@sina.com

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• Oncology

OBJECTIVE: We aimed to identify a reliable biomarker for tongue squamous cell carcinoma (TSCC), the most common oral cancer with no established biomarkers, to predict prognosis and to select the optimal treatment.

MATERIALS AND METHODS: To investigate whether DAPT exhibited antitumor functions, CAL-27 and SCC-9 cells were treated with DAPT (5 µM or 10 µM) for different times. Further, qRT-PCR was used to determine the mRNA expression levels of lncRNA-KAT14 after treatment with DAPT or si-KAT14 and both combined. Moreover, the treated cells were cultured for different times to investigate their antitumor function. The Wound-healing and Transwell assay were carried out to evaluate the migration and invasion viability of cancer cells, respectively. Finally, the Western blots were performed to determine the expression of EMT-related proteins after transfection with si-KAT14 or treatment with DAPT to investigate the effects of DAPT on EMT-related proteins.

RESULTS: Proliferation was inhibited after treatment with DAPT, and the expression of lncRNA-KAT14 was upregulated. To investigate the correlation of DAPT and lncRNA-KAT14 on the metastasis and invasion in tongue cancer, the following cellular processes were assessed: proliferation, invasion, and migration ability. The Western blots were used to determine the expression of E-cadherin, N-cadherin, Vimentin, and Snail, showing that DAPT or lncRNA-KAT14 suppressed all these processes, inducing a decreased expression of N-cadherin, Vimentin, and Snail, and increased expression of E-cadherin, compared with the control group. Once transfection with si-KAT14 occurred, the evaluated cellular processes were enhanced, being this attenuated by the treatment with DAPT.

CONCLUSIONS: Our results suggest that DAPT suppresses invasion and metastasis of tongue cancer by regulating lncRNA-KAT14.

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