LINC00173 blocks GATA6-mediated transcription of COL5A1 to affect malignant development of oral squamous cell carcinoma.

BACKGROUND: Aberrant expression of collagen type V alpha 1 chain (COL5A1) has been linked to several forms of human cancers. In this work, we focused on the interaction of the LINC00173/GATA binding protein 6 (GATA6)/COL5A1 axis in the malignant property of oral squamous cell carcinoma (OSCC) cells.

METHODS: We analyzed six publicly accessible datasets GSE160042, GSE74530, GSE138206, GSE23558, GSE31853 and GSE146483 to identify aberrantly expressed genes in OSCC. The expression of COL5A1 in OSCC tissues and cell lines was examined by RT-qPCR and/or immunohistochemistry. The regulatory mechanism responsible for COL5A1 transcription was predicted via bioinformatics systems, and the interactions of LINC00173, GATA6, and COL5A1 were identified by immunoprecipitation and luciferase assays. Overexpression or downregulation of COL5A1, GATA6, and LINC00173 were induced in OSCC cell lines to determine their roles in the malignant phenotype of the OSCC cells in vitro and in vivo.

RESULTS: COL5A1 showed elevated expression in OSCC tissues and cells. The COLA51 knockdown suppressed proliferation, migration and invasiveness, apoptosis resistance, and pro-angiogenic ability of OSCC cells, and it suppressed the growth and dissemination of xenograft tumors in vivo. GATA6 bound to COL5A1 promoter to activate its transcription, whereas LINC00173 bound to GATA6 to block this transcriptional activation. Overexpression of GATA6 or COL5A1 promoted the malignant phenotype of the OSCC cells, which were blocked upon LINC00173 upregulation.

CONCLUSION: This work demonstrates that LINC00173 blocks GATA6-mediated transcription of COL5A1 to affect malignant development of OSCC.