LINC00704 contributes to the proliferation and accelerates the cell cycle of nasopharyngeal carcinoma cells via regulating ETS1/CDK6 axis.

Abstract

This study is aimed at exploring the biological functions and related mechanism of long noncoding RNA 704 (LINC00704) in the proliferation and cell cycle progression of nasopharyngeal carcinoma (NPC) cells. The expression of LINC00704 in NPC tissues and cells was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). After LINC00704 was overexpressed or knocked down in NPC cell lines, cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine assay, flow cytometry assay, and Transwell assay were adopted to detect the proliferation, cell cycle progression, migration, and invasion of NPC cells. The interaction between LINC00704 and ETS proto-oncogene 1 (ETS1) was verified by bioinformatics analysis, RNA pull-down assay, and RNA immunoprecipitation assay. Dual-luciferase reporter gene assay and chromatin immunoprecipitation followed by qPCR analysis were used to verify the binding status between ETS1 and the promoter region of cyclin-dependent kinase 6 (CDK6). The regulatory effects of LINC00704 and ETS1 on CDK6 expression were detected by Western blot. LINC00704 expression was elevated in NPC tissues and cells, which was significantly correlated with the advanced TNM stage and poor differentiation. LINC00704 overexpression promoted the multiplication, migration, and invasion of NPC cells and blocked the cell cycle progression while knocking down LINC00704 worked oppositely. LINC00704 could bind to ETS1, thus promoting CDK6 transcription. Knocking down LINC00704 inhibited the CDK6 expression in NPC cells. LINC00704 promotes CDK6 transcription by recruiting ETS1 to the promoter region of CDK6, thus promoting the malignant progression of NPC.