Tongue Squamous Cell Carcinoma

LINC00519[LncRNA]

miR-876-3p[miRNA]

MACC1[mRNA]

TSCC tumor cells

Homo sapiens (human)

Onco Targets Ther. 2020 Nov 20;13:11975-11990. doi: 10.2147/OTT.S279798. eCollection 2020.

Long Intergenic Non-Protein Coding RNA 519 Promotes the Biological Activities of Tongue Squamous Cell Carcinoma by Sponging microRNA-876-3p and Consequently Upregulating MACC1.

Cell migration and invasion assay;RNA immunoprecipitation;Luciferase reporter assay;RNA immunoprecipitation;

PURPOSE: Long intergenic non-protein coding RNA 519 (LINC00519) promotes the development of lung squamous cell carcinoma. In this study, we detected the expression of LINC00519 in tongue squamous cell carcinoma (TSCC) and examined its clinical significance. Additionally, the regulatory effects of LINC00519 on behaviors of TSCC tumor cells were explored through functional experiments. Finally, mechanistic studies were performed to elucidate the molecular events underlying the tumor-promoting actions of LINC00519 in TSCC. MATERIALS AND METHODS: The expression of LINC00519 in TSCC tissues and cell lines was determined using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 assay, flow cytometric analysis, cell migration and invasion assays and xenograft tumor model analyses were used to detect TSCC cell proliferation, apoptosis, migration and invasion and in vivo tumor growth, respectively. Mechanistic studies were performed using bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay and rescue experiments. RESULTS: LINC00519 was overexpressed in both TSCC tissues and cell lines. A high LINC00519 level was associated with poor overall survival in patients with TSCC. In vitro, LINC00519 played cancer-promoting roles in TSCC progression by facilitating cell proliferation, migration and invasion and restraining cell apoptosis. In vivo, LINC00519 downregulation resulted in decreased TSCC tumor growth. Mechanistically, LINC00519 acted as a competing endogenous RNA for microRNA-876-3p (miR-876-3p), which directly targets metastasis associated with colon cancer-1 (MACC1), in TSCC cells. LINC00519 upregulated the expression of MACC1 in TSCC cells by sequestering miR-876-3p. Rescue experiments further affirmed that miR-876-3p inhibition or MACC1 overexpression mitigated the inhibitory influences of LINC00519 depletion on cell proliferation, migration and invasion and neutralized the promoting actions of LINC00519 knockdown on cell apoptosis in TSCC. CONCLUSION: LINC00519 aggravated the oncogenicity of TSCC by regulating the miR-876-3p/MACC1 axis. Our findings suggest that the LINC00519/miR-876-3p/MACC1 pathway may be an underlying therapeutic target in TSCC.