Abstract
Multiple studies have unveiled that long non‐coding RNAs (lncRNAs) play a pivotal role in tumour progression and metastasis. However, the biological role of lncRNA ZEB1‐AS1 in oesophageal squamous cell carcinoma (ESCC) remains under investigation, and thus, the current study was to investigate the functions of ZEB1‐AS1 in proliferation and invasion of ESCC. Here, we discovered that ZEB1‐AS1 and ZEB1 were markedly up‐regulated in ESCC tissues and cells relative to their corresponding normal control. ZEB1‐AS1 and ZEB1 overexpressions were both related to TNM staging and lymph node metastasis as well as poor prognosis in ESCC. The hypomethylation of ZEB1‐AS1 promoter triggered ZEB1‐AS1 overexpression in ESCC tissues and cells. In addition, ZEB1‐AS1 knockdown mediated by siRNA markedly suppressed the proliferation and invasion in vitro in EC9706 and TE1 cells, which was similar with ZEB1 siRNA treatment, coupled with EMT alterations including the up‐regulation of E‐cadherin level as well as the down‐regulation of N‐cadherin and vimentin levels. Notably, ZEB1‐AS1 depletion dramatically down‐regulated ZEB1 expression in EC9706 and TE1 cells, and ZEB1 overexpression obviously reversed the inhibitory effects of proliferation and invasion triggered by ZEB1‐AS1 siRNA. ZEB1‐AS1 shRNA evidently inhibited tumour growth and weight, whereas ZEB1 elevation partly recovered the tumour growth in ESCC EC9706 and TE1 xenografted nude mice. In conclusion, ZEB1‐AS1 overexpression is tightly involved in the development and progression of ESCC, and it exerts the antitumour efficacy by regulating ZEB1 level in ESCC.
Highlights
ZEB1‐AS1 functioned as a regulator of ZEB1 gene in ESCC, which was tightly associated with the regulation of proliferation and invasion of ESCC cells
Our data demonstrated that ZEB1‐AS1 and its cognate gene ZEB1 were both unregulated in ESCC tissues, and the up‐regulation of ZEB1‐AS1 and ZEB1 were both associated with TNM staging, lymph node metastasis and poor prognosis of patients with ESCC
Further investigation revealed that ZEB1‐AS1 down‐regulation markedly suppressed cell proliferation and invasion ability of ESCC cells, coupled with EMT suppression, and ZEB1 down‐regulation significantly inhibited cell proliferation and invasion ability of ESCC cells
Summary
Oesophageal cancer (ESCA) is considered as a high malignant neoplasm harbouring two main subtypes: oesophageal adenocarcinoma (EAC) and oesophageal squamous cell carcinoma (ESCC).[1,2]. Long non‐coding RNA (lncRNA) is a group of transcripts longer than 200 nucleotides, which can be split into 6 different types as follows: promoter‐associated transcripts, sense, antisense, bidirectional, intronic, intergenic and 3′UTR‐associated transcripts.[12,13] LncRNAs may be located in the cytoplasm or nucleus, but are mainly present in cell nucleus.[14] LncRNAs are widely involved in the regulation of diverse biological processes.[15,16] In recent years, increasing evidence has revealed the important regulatory roles of lncRNAs in the occurrence and progression of ESCA.[17] Notably, lncRNA‐ miRNA‐mRNA regulatory axis widely participates in oesophageal carcinogenesis.[18] Many lncRNAs play pivotal roles in maintaining and promoting the biological characteristics of tumour cells, and lncRNAs may be the attractive therapeutic targets in a variety of tumours.[19,20] Our recent work identified many differential lncRNA through TCGA database, and we revealed that ZEB1‐AS1 was significantly up‐regulated in ESCA,[21] but its precise functions remain unknown. How ZEB1‐AS1 is regulated during ESCC development is still unclear, and the expression pattern of ZEB1‐AS1 and its regulatory role in the proliferation and invasion ability of ESCC were investigated, which will propose ZEB1‐AS1/ZEB1 regulatory axis as an underlying therapeutic target for ESCC therapy
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