LncRNA MALAT1 Modulates TGF-β1-Induced EMT in Keratinocyte

Abstract

One of the major complications in diabetes is impaired wound healing. Unfortunately, effective therapies are currently lacking. Epithelial to mesenchymal transition (EMT) is a critical process involved in cutaneous wound healing. In response to injury, EMT is required to activate and mobilize stationary keratinocytes in the skin toward the wound bed, which allows for re-epithelialization. This process is stalled in diabetic wounds. In this study, we investigate the role of long non-coding RNA (lncRNA), MALAT1, in transforming growth factor beta 1(TGF-β1)-induced EMT of human keratinocyte (HaCaT) cells. Initially, we detected MALAT1 and TGF-β1 expression in non-diabetic and diabetic wounds and found that these expression are significantly up-regulated in diabetic wounds. Then, HaCaT cells were cultured and exposed to TGF-β1. The EMT of HaCaT cells were confirmed by the increased expression of CDH2, KRT10, and ACTA2, in addition to the down-regulation of CDH1. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 silencing attenuates TGFβ1-induced EMT. Mechanistically, MALAT1 is involved in TGF-β1 mediated EMT through significantly induced ZEB1 expression, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in TGFβ1-induced EMT of human HaCaT cells and provides new understanding for the pathogenesis of diabetic wounds.

LncRNA MALAT1 Regulates Hyperglycemia Induced EMT in Keratinocyte via miR-205

“…However, studies on HG-induced EMT in keratinocytes are lacking. The present study showed that, in HaCaT cells, the mRNA expression of MALAT1 increased when treated with high glucose for 4 and 24 h. Our previous work has demonstrated that in HaCaT cells, MALAT1 is involved in TGF-β1-induced EMT [ 21 ]. Taken together, these results suggest that high glucose induces EMT, possibly via regulating MALAT1 in keratinocytes.…”

“…These studies indicate that MALAT1 has the potential to promote EMT through various pathways. Our recent study demonstrated that MALAT1 is involved in TGF-β1-induced EMT in human keratinocyte (HaCaT) cells via upregulating ZEB1 [ 21 ]. Meanwhile, other studies have shown that MALAT1 can be upregulated under hyperglycemia through multiple pathways [ 22 , 23 , 24 ].…”

The Journey of Cancer Cells to the Brain: Challenges and Opportunities

“…One of its main functions is supporting cancer cell migration through targeting the Rho/ROCK signaling pathway [ 16 , 17 , 18 , 19 ]. MALAT1 can also induce transcription factors, such as ZEB1, leading to TGF-β-mediated EMT in human keratinocytes [ 20 ]. In patients with non-small-cell lung carcinoma (NSCLC), brain metastases and poor prognosis are associated with the presence of MALAT1 in primary tumor samples.…”

The Journey of Cancer Cells to the Brain: Challenges and Opportunities

“…One of its main functions is supporting cancer cells migrtaion through targeting Rho/ROCK signaling pathway [15][16][17] [18]. MALAT1 can also induce transcription factors, such as ZEB1, leading to TGF-β-mediated EMT in human keratinocytes [19]. In patients with non-small cell lung cancer (NSCLC), brain metastases and poor prognosis are associated with the presence of MALAT1 in primary tissues.…”