Downregulation of lncRNA HOTTIP Suppresses the Proliferation, Migration, and Invasion of Oral Tongue Squamous Cell Carcinoma by Regulation of HMGA2-Mediated Wnt/β-Catenin Pathway.

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral tumor. LncRNAs (long noncoding RNAs) and miRNAs (microRNAs) were identified as regulators in many human cancers. This study aims to explore the molecular basis of HOXA transcript at the distal tip (HOTTIP) in regulating OTSCC progression. Materials and Methods: The expression of HOTTIP, miR-124-3p, and high-mobility group AT-hook 2 (HMGA2) was detected by quantitative real-time polymerase chain reaction. Next, the proliferation was evaluated by 3-(4,5-dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) assay. The migration and invasion were assessed by transwell assay. Furthermore, dual-luciferase reporter assay was performed to confirm the combination between HOTTIP and miR-124-3p, miR-124-3p, and HMGA2. Protein levels of HMGA2, β-catenin, c-Myc, and E-cadherin were examined by Western blot. The nude mice model was employed to test the tumor growth in vivo. Results: HOTTIP was upregulated in OTSCC tissues and cells, and was highly expressed in positive lymph node metastasis and late-stage OTSCC patients. Silencing HOTTIP impeded proliferation, migration, and invasion of OTSCC cells. Moreover, HOTTIP knockdown inhibited proliferation, migration, and invasion of OTSCC cells by targeting miR-124-3p. Besides, miR-124-3p targeted HMGA2 to block proliferation, migration, and invasion. HMGA2 could rescue the inhibitory effects of HOTTIP interference on proliferation, migration, and invasion. In addition, HMGA2 overexpression reversed the downregulation of β-catenin and c-Myc protein levels and upregulation of E-cadherin level affected by HOTTIP silencing. Finally, HOTTIP silencing repressed tumor growth and resulted in a great rise on miR-124-3p and E-cadherin expression and a distinct fall on HMGA2, β-catenin, and c-Myc protein levels. Conclusions: HOTTIP knockdown restrained proliferation, migration, and invasion of OTSCC cells by miR-124-3p/HMGA2 axis through Wnt/β-catenin pathway.