Abstract

Esophageal cancer (EC) is a serious malignancy and that is the fifth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main subtype of EC in China. In recent years, long non-coding RNAs (lncRNAs) have demonstrated to be novel tumor-associated regulatory factors. However, the functions and mechanisms of lncRNAs in ESCC have not been fully understood. In this study, we attempted to construct Genome-wide expression profiles of lncRNAs and their potential functions in ESCC. By using microarray, we found a total of 2,366 lncRNAs (1,032 upregulated and 1,334 downregulated) and 3,052 mRNAs (1,477 upregulated and 1,575 downregulated) were differentially expressed between the paired five ESCC tumor tissues and adjacent normal esophageal tissues (fold change, FC ≥2.0 or ≤0.5, p ≤ 0.05). Eight lncRNAs were detected by qRT-PCR to verify the results of the microarray, and the clinicopathological parameters were analyzed in 53 patients with ESCC. GO analysis and KEGG pathway analysis showed that the main biological functions of these abnormal lncRNAs were related to immune response, extracellular vesicular exosome, and protein binding. At the same time, the cis and trans models were used to analyze the potential synergistic regulatory relationship between lncRNAs and their potential target genes. Related genes were the processes that affect cell growth, differentiation, and migration. Then we mapped the lncRNAs-mRNAs co-expression pattern by calculating the PCCs of each lncRNA and mRNA expression value. Furthermore, we investigated the function and potential mechanism of a novel highly expressed lncRNA, lnc-KIAA1244-2, and found that its expression is associated with tumor size, N classification and clinical stage. Knockdown of lnc-KIAA1244-2 inhibited the cell proliferation and inhibited the TNFAIP3 expression in Eca-109 cells. Taken together, the expression patterns of lncRNAs and mRNAs in ESCC tumor tissues are different from those in normal adjacent tissues, and some abnormal expressed lncRNAs may play important roles in the development and progression of ESCC. Lnc-KIAA1244-2 could promote the cell proliferation of ESCC cells and might be a potent therapeutic target for ESCC.

Highlights

  • Esophageal cancer (EC) is a serious malignancy and that is the fifth leading cause of cancer-related death worldwide

  • LncRNA MIR31HG is upregulated in Esophageal squamous cell carcinoma (ESCC) tumor tissues and plasma, which is related to tumor node metastasis (TNM) stage and lymph node metastasis

  • To construct expression profiles of long non-coding RNAs (lncRNAs) in ESCC, we used microarray to detect the expression of lncRNAs, as well as mRNAs in five pairs of ESCC tumor tissues and adjacent normal tissues

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Summary

Introduction

Esophageal cancer (EC) is a serious malignancy and that is the fifth leading cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) have demonstrated to be novel tumor-associated regulatory factors. We investigated the function and potential mechanism of a novel highly expressed lncRNA, lnc-KIAA1244-2, and found that its expression is associated with tumor size, N classification and clinical stage. The expression patterns of lncRNAs and mRNAs in ESCC tumor tissues are different from those in normal adjacent tissues, and some abnormal expressed lncRNAs may play important roles in the development and progression of ESCC. Knockdown of MIR31HG can inhibit the proliferation, migration, invasion, and inhibited the expression of Furin and MMP1 in EC9706 and EC1 cells. It can be used as biomarkers for diagnosis or prediction of ESCC16. The discovery of lncRNAs provides a new strategy to understand the mechanism of tumor occurrence and development

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