miR‑339‑5p negatively regulates loureirin A‑induced hair follicle stem cell differentiation by targeting DLX5

Li,Xiangjun; Wu,Yuqiong; Xie,Fangfang; Zhang,Fengxue; Zhang,Saixia; Zhou,Jianhong; Chen,Dongfeng; Liu,Aijun

doi:10.3892/mmr.2018.9110

miR‑339‑5p negatively regulates loureirin A‑induced hair follicle stem cell differentiation by targeting DLX5

Authors:
- Xiangjun Li
- Yuqiong Wu
- Fangfang Xie
- Fengxue Zhang
- Saixia Zhang
- Jianhong Zhou
- Dongfeng Chen
- Aijun Liu
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Affiliations: Department of Histology and Embryology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China, The Research Centre of Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China, Department of Anatomy, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
Published online on: May 31, 2018 https://doi.org/10.3892/mmr.2018.9110
Pages: 1279-1286
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Our previous study indicated that loureirin A induces hair follicle stem cell (HFSC) differentiation through Wnt/β‑catenin signaling pathway activation. However, if and how microRNAs (miRNAs/miRs) modulate loureirin A‑induced differentiation remains to be elucidated. In the present study, HFSCs were separated from the vibrissae of rats and identified by CD34 and keratin, type 1 cytoskeletal (K)15 expression. Microarray‑based miRNA profiling analysis revealed that miR‑339‑5p was downregulated in loureirin A‑induced HFSC differentiation. miR‑339‑5p overexpression by transfection with miR‑339‑5p mimics markedly inhibited the expression of K10 and involucrin, which are markers of epidermal differentiation, whereas inhibition of miR‑339‑5p by miR‑339‑5p inhibitor transfection promoted the expression of K10 and involucrin. These results suggest that miR‑339‑5p is a negative regulator of HFSC differentiation following induction by loureirin A. These findings were confirmed by a luciferase assay. Homeobox protein DLX‑5 (DLX5) was identified as a direct target of miR‑339‑5p. Furthermore, it was demonstrated that miR‑339‑5p inhibited DLX5. Overexpression of miR‑339‑5p by mimic transfection significantly inhibited protein Wnt‑3a (Wnt3a) expression, while inhibition of miR‑339‑5p by inhibitor transfection significantly increased the expression of Wnt3a. Furthermore, small interfering RNA targeting DLX5 was transfected into HFSCs, and western blot analysis revealed that Wnt3a, involucrin and K10 expression was significantly downregulated. Taken together, these results suggest that miR‑339‑5p negatively regulated loureirin A‑induced HFSC differentiation by targeting DLX5, resulting in Wnt/β‑catenin signaling pathway inhibition. This may provide a possible therapeutic target for skin repair and regeneration.

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