Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Long noncoding RNAs (lncRNAs) have been identified to be associated with many diseases including tumors, and involved in the regulation of a wide array of pathophysiological processes. Small nucleolar RNA host gene 16 (SNHG16), also known as noncoding RNA expressed in aggressive neuroblastoma, was newly identified as a potential oncogene in many cancers. However, its role in ESCC has not been investigated. In the current study, the level of SNHG16 in the ESCC tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR). Then loss-of-function assays were performed to explore the biological effects of SNHG16 in ESCC cell. Based on the online database analysis tools, we uncovered that miR-140-5p could interact with SNHG16 and the level of miR-140-5p was inverse correlated with SNHG16 in ESCC specimens. Moreover, RIP, RNA pulldown system and dual luciferase reporter assay further provided evidence that SNHG16 directly targets miR-140-5p by binding with microRNA binding site harboring in the SNHG16 sequence. Furthermore, bioinformatics analysis revealed that ZEB1 is a target of miR-140-5p in ESCC. Collectively, our findings suggested that SNHG16 could act as an oncogenic lncRNA that promotes tumor progression through acting as an endogenous ‘sponge’ by competing with miR-140-5p, thereby regulating target ZEB1.
Highlights
Esophageal cancer (EC) is one of the most common types of digestive tract cancer [1]
The results revealed an increased Small nucleolar RNA host gene 16 (SNHG16) expression in Esophageal squamous cell carcinoma (ESCC) cells compared with HEEC cells (Figure 1B)
Xia et al revealed that papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/ beta-catenin signaling pathway [28]; Zhang et al demonstrated that H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma [29]; and Austin et al reported that l Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle [30]
Summary
Esophageal cancer (EC) is one of the most common types of digestive tract cancer [1]. About 90% of EC cases in China are esophageal squamous cell carcinoma (ESCC), which is characterized by poor prognosis and high mortality rate [2]. It has been demonstrated that the majority (~97%) of human genome sequences are transcribed into noncoding RNAs (ncRNAs). Among the short ncRNAs, microRNAs are the major member, which have been been demonstrated to play critical roles in ESCC development. Antagonizing miR455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma [8]. LncRNAs, as novel proposed ncRNAs, have been reported to be involved in multiple cancers [9,10,11,12], including ESCC. Transcriptional and posttranscriptional regulation of HOXA13 by lncRNA HOTTIP facilitates tumorigenesis www.impactjournals.com/oncotarget and metastasis in esophageal squamous carcinoma cells [13]
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