LINC00174 Accelerates the Progression of Non-Small Cell Lung Cancer via Modulating EP300/NFAT5 Axis

Abstract

Background: How long non-coding RNA (lncRNA) functions in cancer biology has attracted extensive attention recently. Various lncRNAs interfere with the advancement of non-small cell lung cancer (NSCLC). This work focused on how lncRNA LINC00174 functions in NSCLC. Methods: The analysis of LINC00174 expressions in NSCLC was performed with quantitative real-time PCR (qRT-PCR). The multiplication, migration, aggressiveness and apoptosis of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8), Transwell assays and Flow cytometry. The binding relationship between LINC00174 and E1A-binding protein p300 (EP300) was verified by RNA immunoprecipitation experiment. The binding of EP300 to the promoter region of the nuclear factor of activated T cells 5 (NFAT5) was detected by dual luciferase reporter gene assay and immunocoprecipitation assay. Results: The expression of LINC00174 was increased in NSCLC, which impaired the overall survival time in patients with NSCLC. Knocking down LINC00174 curbed the multiplication, migration and aggressiveness of cancer cells and promoted apoptosis. LINC00174 was directly combined with EP300. Knocking down LINC00174 inhibited the binding of EP300 and NFAT5 promoter region, thereby curbing NFAT5 transcription. In addition, NFAT5 overexpression facilitated cancer cell malignancy, which could be reversed by knockdown of LINC00174. Conclusions: This study indicates that LINC00174 promotes NFAT5 transcription by recruiting the EP300 to NFAT5 promoter region, thereby accelerating the progression of NSCLC.