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

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 {"type":"entrez-nucleotide","attrs":{"text":"AC048380.1","term_id":"7549714","term_text":"AC048380.1"}}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, {"type":"entrez-nucleotide","attrs":{"text":"AC048380.1","term_id":"7549714","term_text":"AC048380.1"}}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.