Comparison of long non‑coding RNAs, microRNAs and messenger RNAs involved in initiation and progression of esophageal squamous cell carcinoma

Abstract

Traditionally, cancer research has focused on protein‑coding genes, which are considered the principal effectors and regulators of tumorigenesis. Non‑coding RNAs, in particular microRNAs (miRNAs) and long non‑coding RNAs (lncRNAs), have been widely reported to be important in the regulation of tumorigenesis and cancer development. However, to the best of our knowledge, investigation of the expression profiles of lncRNAs and a comparison of the involvement of lncRNAs, miRNAs and messenger RNAs (mRNAs) in esophageal tumorigenesis and development have not previously been performed. In the current study, intrinsic associations among the expression profiles of lncRNAs, miRNAs and mRNAs from normal esophageal tissues and those from cancer tissues were investigated. Oligonucleotide microarrays were used to detect the expression profiles of the three types of RNA in the canceration processes of human esophageal squamous cell carcinoma (ESCC) tissues. It was demonstrated that the different RNAs exhibit associated patterns of expression among normal esophageal epithelium, low‑grade intraepithelial neoplasia (LGIN), high‑grade intraepithelial neoplasia (HGIN), and carcinoma tissues, particularly in the critical period of canceration (HGIN to ESCC). Furthermore, the results indicated a high level of similarity in the potential function of lncRNAs, miRNAs and mRNAs in the processes of ESCC development. In the current study, a first generation atlas of lncRNA profiling and its association with miRNAs and mRNAs in the canceration processes of ESCC were presented.

Figure 1

Initiation and progression of esophageal squamous cell carcinoma.

Figure 2

Venn diagrams presenting the differential expression of mRNAs, miRNAs and lncRNAs. Comparison of the numbers of (A) lncRNAs, (B) miRNAs and (C) mRNAs differentially expressed in each disease stage (stages 2–5) vs. the normal controls (stage 1). lncRNA, long non-coding RNA; miRNA, microRNA; mRNA, messenger RNA.

Figure 3

Microarray heatmaps presenting the differential expression of (A) lncRNAs, (B) miRNAs and (C) mRNAs in disease stages (stages 2–5) compared with normal controls (stage 1). Top diagrams represent the union set (all RNAs differentially expressed in at least one disease stage vs. the normal control), and bottom diagrams represent the intersection set (RNAs which were differentially expressed in every disease stage vs. the normal control). Blue represents downregulated genes, and red represents upregulated genes. lncRNA, long non-coding RNA; miRNA, microRNA; mRNA, messenger RNA.

Figure 4

Cross-linked diagram of the similar potential functions among (A) miR1470 and (B) miR361-3p mRNAs and lncRNAs in the initiation and progression of ESCC. Green represents downregulated genes, red represents upregulated genes, and different quadrants represent different stages of the disease as indicated. mRNA, messenger RNA; lncRNA, long non-coding RNA; ESCC, esophageal squamous cell carcinoma.

Figure 5

Functions of dysregulated (A) lncRNAs, (B) miRNAs (miR1470 and miR361-3p) and (C) mRNAs in the initiation and progression of ESCC. The dysregulated RNAs consist of those differentially expressed between the disease stages (stages 2–5) and the normal controls (stage 1). Blue represents downregulated genes, and red represents upregulated genes. lncRNA, long non-coding RNA; miRNA, microRNA; mRNA, messenger RNA; ESCC, esophageal squamous cell carcinoma.