LncRNA HOXA11-AS Aggravates Keloid Progression by the Regulation of HOXA11-AS-miR-205-5p-FOXM1 Pathway

Background: Keloid is troublesome for patients' skin appearance and mental health, although it is a benign tumor. Long noncoding RNA (lncRNA) troubling keloid is frequently reported. The purpose of this study was to investigate the role of lncRNA homeobox (HOX) A11 anti-sense (HOXA11-AS) and related action mechanisms during the development of keloid. Methods: The expression of HOXA11-AS, miR-205-5p, and forkhead box M1 (FOXM1) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation or apoptosis was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium (MTT) assay or flow cytometry assay. Cell migration and invasion were monitored by transwell assay. The protein levels of extracellular matrix (ECM) proteins (collagen I and collagen III), fibronectin, glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and FOXM1 were quantified by Western blot. Glycolysis processes were investigated by the glycolysis stress test, glucose consumption, and lactate production. The relationship between miR-205-5p and HOXA11-AS or FOXM1 was predicted by the online tool MlRcode or starBase v2.0 and verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP). Results: HOXA11-AS and FOXM1 were significantly upregulated in keloid tissues and keloid fibroblasts, while miR-205-5p was downregulated. HOXA11-AS knockdown or miR-205-5p enrichment inhibited proliferation, migration, invasion, ECM accumulation, and glycolysis but accelerated apoptosis of keloid fibroblasts. MiR-205-5p was targeted by HOXA11-AS, and its inhibition overturned the effects of HOXA11-AS knockdown. Moreover, FOXM1 was a target of miR-205-5p, and HOXA11-AS regulated the expression of FOXM1 by adsorbing miR205-5p. FOXM1 overexpression abolished the role of miR-205-5p enrichment. Conclusions: The HOXA11-AS-miR-205-5p-FOXM1 pathway may be an active mode in which HOXA11-AS participates in the progression of keloid. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study identified that the HOXA11-AS-miR-205-5p-FOXM1 pathway plays a role in the progression of keloid, indicating a potential mechanism for therapeutic intervention in keloid management.