Abstract
Epithelial-to-mesenchymal transition (EMT) is critical to cutaneous wound healing. When skin is injured, EMT activates and mobilizes keratinocytes toward the wound bed, therefore enabling re-epithelialization. This process becomes dysregulated in patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) regulate many biological processes. LncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) influences numerous cellular processes, including EMT. The objective of the current study is to explore the role of MALAT1 in hyperglycemia (HG)-induced EMT. The expression of MALAT1 was found to be significantly upregulated, while the expression of miR-205 was downregulated in diabetic wounds and high-glucose-treated HaCaT cells. The initiation of EMT in HaCaT cells from hyperglycemia was confirmed by a morphological change, the increased expression of CDH2, KRT10, and ACTA2, and the downregulation of CDH1. The knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 and miR-205 were found to modulate HG-induced EMT. MALAT1 silencing or miR-205 overexpression appears to attenuate hyperglycemia-induced EMT. Mechanistically, MALAT1 affects HG-induced EMT through binding to miR-205 and therefore inducing ZEB1, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in the hyperglycemia-induced EMT of human HaCaT cells. This provides a new perspective on the pathogenesis of diabetic wounds.