High‑throughput sequencing reveals differentially expressed lncRNAs and circRNAs, and their associated functional network, in human hypertrophic scars

Abstract

Growing evidence suggests that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in the occurrence and development of tumors and fibrotic diseases. However, the integrated analysis of lncRNA and circRNA expression, alongside associated co-expression and competing endogenous RNA (ceRNA) networks, has not yet been performed in human hypertrophic scars (HS). The present study compared the expression levels of lncRNAs, circRNAs and mRNAs in human HS and normal skin tissues by high-throughput RNA sequencing. Numerous differentially expressed lncRNAs, circRNAs and mRNAs were detected. Subsequently, five aberrantly expressed lncRNAs and mRNAs, and six circRNAs were measured to verify the RNA sequencing results by reverse transcription-quantitative polymerase chain reaction. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the dysregulated genes, in order to elucidate their principal functions. In addition, a coding-noncoding gene co-expression (CNC) network and ceRNA network were constructed for specific significantly altered genes. The CNC network analysis suggested that AC048380.1 and LINC00299 were associated with metastasis-related genes, including inhibin subunit βA (INHBA), SMAD family member 7 (SMAD7), collagen type I α1 chain (COL1A1), transforming growth factor β3 (TGFβ3) and MYC proto-oncogene, bHLH transcription factor (MYC). Inhibitor of DNA binding 2 was associated with the lncRNAs cancer susceptibility 11, TGFβ3-antisense RNA 1 (AS1), INHBA-AS1, AC048380.1, LINC00299 and LINC01969. Circ-Chr17:50187014_50195976_-, circ-Chr17:50189167_50194626_-, circ-Chr17:50189167_ 50198002_- and circ-Chr17:50189858_50195330_- were also associated with INHBA, SMAD7, COL1A1, TGFβ3 and MYC. COL1A1 and TGFβ3 were associated with circ-Chr9:125337017_125337591_+ and circ-Chr12:120782654_120784593_-. The ceRNA network indicated that INHBA-AS1 and circ-Chr9:125337017_125337591_+ were ceRNAs of microRNA-182-5p targeting potassium voltage-gated channel subfamily J member 6, ADAM metallopeptidase with thrombospondin type 1 motif 18, SRY-box 11, MAGE family member L2, matrix metallopeptidase 16, thrombospondin 2, phosphodiesterase 11A and collagen type V a1 chain. These findings suggested that lncRNAs and circRNAs may act as ceRNAs, which are implicated in the pathophysiology and development of human HS, and lay a foundation for further insight into the novel regulatory mechanism of lncRNAs and circRNAs in hypertrophic scarring.

A Long Noncoding RNA (lncRNA)-Associated Competing Endogenous RNA (ceRNA) Network Identifies Eight lncRNA Biomarkers in Patients with Osteoarthritis of the Knee

“…Previous studies have shown that dysregulated ceRNAs contributed to the abnormal transcriptome [30]. Therefore, the expression pattern of lncRNAs and mRNAs in the ceRNA-ceRNA interaction network in OA of the knee were investigated.…”

CircRNA_100395 inhibits cell proliferation and metastasis in ovarian cancer via regulating miR-1228/p53/epithelial-mesenchymal transition (EMT) axis

“…Circular RNAs (circRNAs), firstly identified in RNA virus and later observed in eukaryotic cells as an endogenous RNA splicing product, are a class of non-coding RNAs with covalently bonded circular structure, but without 5′ caps and 3′ tails [5,6]. Thanks to the development of high-throughput sequencing, molecular biology techniques and bioinformatics, the expression patterns and diverse functions of circRNAs are being elucidated [7,8]. They participated in multiple physiological and pathological processes through sponging miRNAs and other RNAs by base pairing, interacting with proteins by their three-dimensional structure with a high degree of tissue-specific expression [9,10], while increasing studies indicated that non-coding RNAs (ncRNAs) was closely related to the tumorigenesis [11,12].…”

Identification of Long Noncoding RNA Associated ceRNA Networks in Rosacea

“…Dysregulation of lncRNAs has been reported to be associated with several human diseases, including autoimmune diseases and different types of tumors [7,8,21,[36][37][38][39]. Recently, lncRNAs broad expression in cutaneous disorders including systemic lupus erythematosus (SLE), sensitive skin, psoriasis, and aging process has been documented [40][41][42][43].…”