LINC00514 promotes lipogenesis and tumor progression in esophageal squamous cell carcinoma by sponging miR-378a-5p to enhance SPHK1 expression

Increasing evidence has demonstrated that long non-coding RNAs serve pivotal roles in tumor development, progression, metastasis and metabolism. However, to the best of our knowledge, the roles and molecular mechanisms of long intergenic nonprotein-coding RNA 00514 (LINC00514) in esophageal squamous cell carcinoma (ESCC) remain unknown. The present study found that LINC00514 and sphingosine kinase 1 (SPHK1) were both upregulated in ESCC tissues and cells, and their high expression levels were closely associated with Tumor-Node-Metastasis stage, lymph node metastasis and poor prognosis of patients with ESCC. Functionally, knockdown of LINC00514 inhibited cell proliferation and invasion, and led to the downregulation of lipogenesis-related proteins, including SPHK1, fatty acid synthase, acetyl-coenzyme (Co)A carboxylase α and stearoyl-CoA desaturase 1, whereas LINC00514 overexpression promoted cell proliferation and invasion in ESCC KYSE150 and KYSE30 cells, and upregulated expression of lipogenesis-related proteins. Mechanistically, LINC00514 functioned as a competing endogenous RNA by sponging microRNA (miR)-378a-5p, resulting in the upregulation of SPHK1, which was accompanied by the activation of lipogenesis-related pathways, to promote ESCC cell proliferation and invasion. Taken together, these findings suggest that LINC00514 may participate in ESCC lipogenesis, and targeting the LINC00514/miR-378a-5p/SPHK1 signaling axis may be a novel and promising therapeutic strategy for management of patients with ESCC.