Abstract
OBJECTIVE:The long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) exerts vital regulatory functions in diverse tumors. However, the biological function of KCNQ1OT1 in esophageal squamous cell carcinoma (ESCC) remains unclear.METHODS:KCNQ1OT1 expression was detected in ESCC tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were detected by the CCK-8 assay, EdU assay, flow cytometry analysis, and Transwell experiments, respectively. Bioinformatics analysis, luciferase reporter experiments, and RNA immunoprecipitation assays were used to predict and validate the regulatory relationships between KCNQ1OT1, microRNA-133b (miR-133b) and epidermal growth factor receptor (EGFR).RESULTS:KCNQ1OT1 expression was remarkably upregulated in ESCC tissues and cell lines. Overexpression of KCNQ1OT1 markedly promoted ESCC cell proliferation, migration, and invasion and enhanced the expression of N-cadherin, MMP-2, and MMP-9, but inhibited apoptosis and E-cadherin expression in ESCC cell lines; KCNQ1OT1 knockdown exerted the opposite effects. KCNQ1OT1 could directly bind to miR-133b and suppress its expression, and miR-133b reversed the effects of KCNQ1OT1 overexpression in ESCC cells. MiR-133b reduced the expression of epidermal growth factor receptor (EGFR); further, KCNQ1OT1 activated the phosphatidylinositol 3-kinase/AKT serine/threonine kinase 1 (PI3K/AKT) signaling pathway by repressing miR-133b repression and indirectly upregulating EGFR. KCNQ1OT1 expression was positively correlated with EGFR mRNA expression and negatively correlated with miR-133b expression.CONCLUSION:KCNQ1OT1 facilitates ESCC progression by sponging miR-133b and activating the EGFR/PI3K/AKT pathway.
Highlights
Esophageal cancer (EC) is one of the most common gastrointestinal malignancies worldwide [1]
The results suggested that the mRNA expression levels of both KCNQ1OT1 and epidermal growth factor receptor (EGFR) were increased, whereas miR-133b expression was decreased in Esophageal squamous cell carcinoma (ESCC) tissues (Figure 1B–D)
KCNQ1OT1 is transcribed by RNA polymerase II in an antisense direction from a highly conserved and differentially methylated region (KCNQ1ICR, KvDMR, or IC2) in intron 10 of the KCNQ1 gene, and KCNQ1OT1 interacts with chromatin to regulate the transcription of several genes in an epigenetic manner, playing important roles in the tumorigenesis and development of various cancers [25,26]
Summary
Esophageal cancer (EC) is one of the most common gastrointestinal malignancies worldwide [1]. Esophageal squamous cell carcinoma (ESCC) is the main pathological type of EC and is one of the leading causes of cancer-associated deaths worldwide [2]. The 5-year survival rate of ESCC patients is only about 19%, and the median survival time of patients with advanced ESCC is less than 1 year [3,4,5]. It is necessary to study the molecular mechanism underlying the pathogenesis of ESCC and identify therapeutic targets for improving patient prognosis.
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