%0 Journal Article
%T MicroRNA-21 Regulates hTERT via PTEN in Hypertrophic Scar Fibroblasts
%A Hua-Yu Zhu
%A Chao Li
%A Wen-Dong Bai
%A Lin-Lin Su
%A Jia-Qi Liu
%A Yan Li
%A Ji-Hong Shi
%A Wei-Xia Cai
%A Xiao-Zhi Bai
%A Yan-Hui Jia
%A Bin Zhao
%A Xue Wu
%A Jun Li
%A Da-Hai Hu
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0097114
%X Background As an important oncogenic miRNA, microRNA-21 (miR-21) is associated with various malignant diseases. However, the precise biological function of miR-21 and its molecular mechanism in hypertrophic scar fibroblast cells has not been fully elucidated. Methodology/Principal Findings Quantitative Real-Time PCR (qRT-PCR) analysis revealed significant upregulation of miR-21 in hypertrophic scar fibroblast cells compared with that in normal skin fibroblast cells. The effects of miR-21 were then assessed in MTT and apoptosis assays through in vitro transfection with a miR-21 mimic or inhibitor. Next, PTEN (phosphatase and tensin homologue deleted on chromosome ten) was identified as a target gene of miR-21 in hypertrophic scar fibroblast cells. Furthermore, Western-blot and qRT-PCR analyses revealed that miR-21 increased the expression of human telomerase reverse transcriptase (hTERT) via the PTEN/PI3K/AKT pathway. Introduction of PTEN cDNA led to a remarkable depletion of hTERT and PI3K/AKT at the protein level as well as inhibition of miR-21-induced proliferation. In addition, Western-blot and qRT-PCR analyses confirmed that hTERT was the downstream target of PTEN. Finally, miR-21 and PTEN RNA expression levels in hypertrophic scar tissue samples were examined. Immunohistochemistry assays revealed an inverse correlation between PTEN and hTERT levels in high miR-21 RNA expressing-hypertrophic scar tissues. Conclusions/Significance These data indicate that miR-21 regulates hTERT expression via the PTEN/PI3K/AKT signaling pathway by directly targeting PTEN, therefore controlling hypertrophic scar fibroblast cell growth. MiR-21 may be a potential novel molecular target for the treatment of hypertrophic scarring.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0097114