Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways

Abstract

Background/Aims: Long non-coding RNAs (lncRNAs) are thought to play crucial roles in human diseases. However, the function of lncRNAs in hypertrophic scar formation remains poorly understood. Methods: Utilizing qRT-PCR, we explored the expression changes of AC067945.2. Overexpression of AC067945.2 in normal skin fibroblasts was performed by transient plasmid transfection. Western blot was used to check the proteins' expression changes. Cell Counting Kit-8 (CCK-8) assay and Annexin V/7-AAD staining were used to examine cell proliferation and apoptosis, respectively. mRNA-seq was applied to dissect the differentially expressed mRNAs in AC067945.2 overexpressed cells. We also performed ELISA to detect the VEGF secretion. Results: AC067945.2 was down-regulated in hypertrophic scar tissues. Overexpression of AC067945.2 did not affect cell proliferation, but it mildly promoted early apoptosis in normal skin fibroblasts. Furthermore, AC067945.2 overexpression inhibited the expression of COL1A1, COL1A2, COL3A1 and α-SMA proteins. Transforming growth factor-β1 (TGF-β1) could inhibit the expression of AC067945.2. Based on mRNA-seq data, compared with mRNAs in the control group, 138 mRNAs were differentially expressed, including 14 upregulated and 124 down-regulated transcripts, in the AC067945.2 overexpression group. Gene ontology and pathway analyses revealed that AC067945.2 overexpression was correlated with developmental processes, binding, extracellular region, and the vascular endothelial

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases

“…A study by Chen et al (2018) investigated the role of long non-coding RNAs (lncRNAs) in hypertrophic scars and found that one lncRNA had lower levels (Chen et al, 2018). In cultured skin fibroblasts overexpressing this same lncRNA reduced COL3A1 mRNA levels.…”

Long non‐coding RNAs in cutaneous biology and proliferative skin diseases: Advances and perspectives

“…Mechanistically, AC067945.2 can significantly promote early apoptosis and reduce the expression of COL1A1, COL1A2, COL3A1 and α‐SMA in normal skin fibroblasts. Therefore, downregulated AC067945.2 in hypertrophic scar tissues contributed to the pathological hypertrophic scar formation via inhibiting fibroblast apoptosis and promoting extracellular matrix deposition …”

<p>Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence</p>

“…52,53 In skin fibroblasts, lncRNA AC067945.2 overexpression inhibited the expression of COL1A1, COL1A2, COL3A1. 54 Cao et al demonstrated that lncRNA PVT1 promotes atrial fibrillation by increasing collagen expression via the miR-128-3p-SP1-TGF-β1-Smad axis in atrial fibroblasts. 55 In this study, we identified a complex regulatory network of extracellular matrix-related genes, lncRNAs and miRNAs in the process of LGG recurrence.…”