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

Abstract

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.

LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/β-catenin signaling pathway

“…Another study demonstrated that LINC00514 in the nucleus of papillary thyroid cancer cells promotes tumor progression by elevating CD23 expression [ 14 ]. Similar trends have been reported in tumors, such as cervical cancer [ 15 ], triple-negative breast cancer [ 16 , 17 ], osteosarcoma [ 18 ], and esophageal cancer [ 19 ], but not in NSCLC.…”

Depicting the Implication of miR-378a in Cancers

“…126 LINC00514, acting as a ceRNA, upregulates SPHK1 by sponging miR-378a-5p and activates adipogenesisrelated pathways, thereby promoting the proliferation and invasion of ESCC cells. 127 In a RMS-derived cell line, miR-378a upregulation inhibited IGF1R expression and impacted phosphorylated-Akt protein levels. 51 Moreover, ectopic expression of miR-378a modulated apoptosis, cell migration, cytoskeleton organization, and the expression of the muscle markers MyoD1, MyoR, desmin, and MyHC in RMS.…”

“… 126 LINC00514, acting as a ceRNA, upregulates SPHK1 by sponging miR-378a-5p and activates adipogenesis-related pathways, thereby promoting the proliferation and invasion of ESCC cells. 127 …”

LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4

“…Cytoplasmic lncRNAs can competitively bind miRNAs and regulate miRNA target genes at the posttranscriptional level (8). A large amount of literature has shown that lncRNAs play a regulatory role in the development of ESCC (9)(10)(11). In this study, the differentially expressed lncRNA FOXP4-AS1 was screened by the microarrays.…”