Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma

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.

Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma

“…The gene expression matrix of GSE120356 was used to calculate the Pearson correlation coefficient (Ma et al, 2019c). Based on the ceRNA mechanism, the two RNAs of the ceRNA pair have a co-expression effect, which can be well supported for subsequent analysis.…”

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

“…A large proportion of human genome encodes for the long non-coding RNAs (lncRNAs), a diverse set of transcripts that do not encode for any functional protein. LncRNA transcripts are larger than 200 nucleotides in length and include, intronic lncRNA, long intergenic non-coding RNAs (lincRNAs), pseudogenic transcripts, circular RNAs (circRNA), long enhancer noncoding RNAs (eRNAs), natural antisense transcripts (NATs), and transcribed ultra-conserved regions (TUCRs) [ 1 , 2 ]. Studies have shown that lncRNAs play crucial role in various biological processes including gene regulation, gene transcription, post-transcriptional modification, and chromatin remodeling in health and disease [ 3 , 4 ].…”

LncRNA GACAT3 promotes esophageal squamous cell carcinoma progression through regulation of miR-149 /FOXM1

“…Total protein extraction from cells utilized the RIPA buffer (Beyotime, China) containing protease inhibitors (Roche, Switzerland). Immunoblot was performed as previously described [17]. Anti-rabbit antibodies against FOXM1 (1:500, ZENbio, China) were used as primary antibodies.…”