Abstract

The aim of the present study was to investigate the expression of long non-coding(lnc) RNA-extracellular matrix (ECM) in esophageal squamous cell carcinoma (ESCC) and its effect on ESCC metastasis. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the expression of lncRNA-ECM in ESCC tissues was investigated and compared with that in corresponding adjacent tissues. In addition, the expression of lncRNA-ECM in the human ESCC cell lines TE-1, EC9706, KYSE150, Eca109 and KYSE30 was also detected and compared with that in the normal esophageal mucosal epithelial cell line HET-1A. The clinicopathological association between lncRNA-ECM and ESCC was assessed. Silencing and overexpression of lncRNA-ECM in ESCC TE-1 and Eca109 cells determined the correlation between lncRNA-ECM expression and ESCC invasion and metastasis. The possible target genes of lncRNA-ECM were predicted and verified by bioinformatics analysis and experimental results. The expression level of intercellular adhesion molecule 1 (ICAM1) was detected in ESCC tissues by RT-qPCR and the correlation between the expression of ICAM1 and lncRNA-ECM was analyzed. Changes in the expression of ICAM1 in ESCC TE-1 and Eca109 cell lines were evaluated after knocking down lncRNA-ECM and transfection of lncRNA-ECM overexpression plasmids. The expression level of lncRNA-ECM in the tissues of ESCC with lymph node metastasis were significantly increased compared with ESCC with no lymph metastasis (P<0.05). LncRNA-ECM silencing notably reduced the invasion and metastasis of TE-1 and Eca109 cells, while lncRNA-ECM overexpression promoted the invasion and metastasis of the two cell lines. The expression level of ICAMI was directly correlated with the expression of lncRNA-ECM, suggesting that ICAM1 may be the downstream target gene of lncRNA-ECM. LncRNA-ECM was revealed as being overexpressed in ESCC. LncRNA-ECM expression was positively correlated with metastasis and may affect the metastasis of ESCC through ICAMI regulation. These findings indicate that lncRNA-ECM may be promising as a novel biomarker for the diagnosis and prediction of prognosis for ESCC, and it may also serve as a novel therapeutic target for ESCC.

Highlights

  • Esophageal cancer is one of the most common malignancies, with an incidence rate that ranks sixth in China and fourth among the causes of cancer‐related mortality [1]

  • LncRNA‐extracellular matrix (ECM) expression was positively correlated with metastasis and may affect the metastasis of Esophageal squamous cell carcinoma (ESCC) through ICAMI regulation. These findings indicate that lncRNA‐ECM may be promising as a novel biomarker for the diagnosis and prediction of prognosis for ESCC, and it may serve as a novel therapeutic target for ESCC

  • Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we found that lncRNA‐ECM and its potential target genes are closely associated with cell cycle regulation, cell differentiation and other processes (Fig. 2A‐C), including extracellular matrix receptor interaction, cell cycle regulation, adhesive junctions, and other multiple signaling pathways associated with cancer (Fig. 2D), and it may be involved in the pathogenesis of ESCC

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Summary

Introduction

Esophageal cancer is one of the most common malignancies, with an incidence rate that ranks sixth in China and fourth among the causes of cancer‐related mortality [1]. Esophageal cancer is one of the most common lethal tumors worldwide with the sixth highest mortality rate [2]. The metastasis of ESCC is the main cause of poor prognosis and mainly involves lymph node and distant metastasis [3]. Previous studies demonstrated that the 5‐year survival rate of ESCC patients without metastasis was 70‐92%, whereas it was only 18‐47% in those with metastasis [3,4].

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