EZH2-mediated suppression of lncRNA-LET promotes cell apoptosis and inhibits the proliferation of post-burn skin fibroblasts

Zheng,Weicai; Yu,Aixiang

doi:10.3892/ijmm.2018.3425

EZH2-mediated suppression of lncRNA-LET promotes cell apoptosis and inhibits the proliferation of post-burn skin fibroblasts

Authors:
- Weicai Zheng
- Aixiang Yu
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Affiliations: Department of Burns and Plastic Surgery, The First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
Published online on: January 25, 2018 https://doi.org/10.3892/ijmm.2018.3425
Pages: 1949-1957
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although the upregulation of enhancer of zeste homolog 2 (EZH2) expression and downregulation of long non-coding RNA (lncRNA) LET expression are known to be associated with cell apoptosis and proliferation, little is known about the interaction of EZH2 with lncRNA LET. The present study aimed to investigate the interaction of EZH2 and lncRNA LET, and the mechanism of human dermal fibroblast (HDF) proliferation and apoptosis. Tissue samples from 33 burn patients with second- and third-degree burns and 8 controls were collected. mRNA was extracted from the burn tissues for analysis. Isolated primary HDFs were treated with heat or transfected with LET overexpression vectors, and the cell functions and associated proteins in the HDFs were analyzed. Decreased lncRNA LET expression was detected in burn tissues compared with normal skin. Heat-treated HDFs exhibited a reduction in lncRNA LET expression and increase in EZH2 expression. LET gain‑of‑function experiments in primary HDFs revealed increases in cell proliferation, the proportion of cells in the S stage, and cyclin D1 and cyclin‑dependent kinase 4 (CDK4) expression, and reductions in the percentage of apoptotic cells, the Bax/Bcl-2 ratio and caspase-3 expression. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated the interaction of ZH2 with lncRNA LET, and of EZH2 with H3K27me3 in HDFs. Furthermore, a negative correlation between lncRNA LET and EZH2 expression was identified. It may be concluded that increased lncRNA-LET expression promoted cell proliferation and inhibited cell apoptosis via the cyclin D1-CDK4 and Bax/Bcl-2/caspase-3 signaling pathways, respectively. Furthermore, the inhibition of lncRNA LET may be regarded as an option for use in the healing of burns.

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