Trichostatin A‑induced miR‑30a‑5p regulates apoptosis and proliferation of keloid fibroblasts via targeting BCL2
Autor: | Xing-Hua Gao, Yunlin Wang, Shuang Chen, Chundi He, Hong-Duo Chen, Le Qu, Qing Zhao, Qianlei Zou, Xiaoqing Jian |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition keloid fibroblast Cell Apoptosis Biology Hydroxamic Acids Biochemistry 03 medical and health sciences 0302 clinical medicine Keloid microRNA Genetics medicine Cluster Analysis Humans B-cell lymphoma 2 skin and connective tissue diseases 3' Untranslated Regions Molecular Biology Cell Proliferation Skin Oncogene Cell growth microRNA-30a-5p Antagomirs Articles Fibroblasts Cell cycle medicine.disease G2 Phase Cell Cycle Checkpoints Histone Deacetylase Inhibitors MicroRNAs 030104 developmental biology medicine.anatomical_structure Trichostatin A Proto-Oncogene Proteins c-bcl-2 Oncology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Collagen Signal transduction medicine.drug |
Zdroj: | Molecular Medicine Reports |
ISSN: | 1791-3004 1791-2997 |
DOI: | 10.3892/mmr.2019.10185 |
Popis: | Keloids are benign fibrous overgrowths that occur as a result of abnormal wound healing following cutaneous injury. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that serve critical roles in numerous important biological processes, such as cell proliferation, differentiation and apoptosis. However, their role in keloid development remains largely unknown. In the present study, the role of miR-30a-5p, a miRNA regulated by Trichostatin A (TSA), in apoptosis within cultured keloid fibroblasts was investigated. An MTT assay was used to detect the proliferation of cultured keloid fibroblasts treated with TSA. Cell apoptosis and cell cycle phases were analyzed using flow cytometry. In addition, an miRNA microarray was performed to compare expression profiles between cultured keloid fibroblasts treated with or without 1,000 nM TSA. Reverse transcription-quantitative polymerase chain reaction analysis was conducted to estimate miRNA expression levels. The direct target of miR-30a-5p was identified using a dual-luciferase reporter assay. Western blotting was employed to assess protein expression levels in keloid fibroblasts. The results demonstrated that TSA inhibited the proliferation of keloid fibroblasts in a time- and dose-dependent manner. The miRNA microarray revealed alterations in the expression of numerous miRNA sequences in response to TSA when compared with controls. Notably, the expression of miR-30a-5p was downregulated in keloid tissues. In addition, overexpression of miR-30a-5p induced apoptosis by targeting B-cell lymphoma 2, which was similar to that observed in response to TSA. These results provide important information regarding a novel miR-30a-5p-mediated signaling pathway induced by TSA treatment, and suggest a potential use for TSA and miR-30a-5p as effective therapeutic strategies for keloids. |
Databáze: | OpenAIRE |
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