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03 February 2020 : Laboratory Research  

Knockdown of Long Non-Coding RNA (lncRNA) Colon Cancer-Associated Transcript-1 (CCAT1) Suppresses Oral Squamous Cell Carcinoma Proliferation, Invasion, and Migration by Inhibiting the Discoidin Domain Receptor 2 (DDR2)/ERK/AKT Axis

Mingyu Sun1ABEF, Zhenyu Shen1ABC*

DOI: 10.12659/MSM.920020

Med Sci Monit 2020; 26:e920020

Abstract

BACKGROUND: Emerging evidence shows that lncRNAs are involved in carcinogenesis or suppression in diverse cancers. This study assessed the biological role of lncRNA CCAT1 in OSCC and explored the underlying molecule mechanism.

MATERIAL AND METHODS: CCAT1 and DDR2 expression was measured by qRT-PCR. Colony formation assay and CCK-8 assay were performed to evaluate cell proliferation. Cell cycle was determined by flow cytometric analysis and Western blot analysis. In addition, wound healing and Transwell assay were used to assess cell migration and invasion, respectively. RNA immunoprecipitation (RIP) assay were employed to identify the interaction between DDR2 and CCAT1. Protein levels involved in DDR2/ERK/AKT pathway were estimated by Western blot assay.

RESULTS: The findings revealed that CCAT1expression was upregulated in OSCC cell lines. Knockdown of CCAT1 repressed cell proliferation, blocked the cell cycle, and suppressed the invasion and migration of TCA-8113 cells. Moreover, DDR2 expression in OSCC cell lines was downregulated and CCAT1 silencing repressed the expression of DDR2. RIP assays validated the binding of CCAT1 and DDR2 protein. Moreover, CCAT1 silencing suppressed the ERK/AKT signaling through DDR2 in TCA-8113 cells.

CONCLUSIONS: Downregulation of CCAT1 suppressed TCA-8113 cell proliferation, invasion, and migration by inactivation of the ERK/AKT pathway via inhibition of DDR2, suggesting the value of CCAT1 in diagnosis and treatment of patients with OSCC.

Keywords: Mouth Neoplasms, Carcinoma, Squamous Cell, Cell Cycle, Discoidin Domain Receptor 2, Gene Silencing, Protein Binding, Proto-Oncogene Proteins c-akt

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750