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miR-4417 suppresses keloid fibrosis growth by inhibiting CyclinD1

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Abstract

Mounting evidence has reported that microRNAs (miRNAs) play irreplaceable roles in the development of keloid fibrosis. miR-4417 has been reported to contribute to nickel chloride-promoted lung epithelial cell fibrogenesis and tumorigenesis. However, whether miR-4417 is involved in keloid fibrogenesis as well as its underlying mechanisms remain largely elusive. In this study, the expression levels of miR-4417 and CyclinD1 in keloid tissues and fibroblasts were examined by qRT-PCR. Cell proliferation was determined by CCK assay. Western blot and flow cytometry were performed to evaluate cell apoptosis. Cell migration and invasion were measured by Transwell assay. Luciferase reporter assay was used to confirm the relationship between miR-4417 and CyclinD1. As a result, we found that miR-4417 was significantly down-regulated in keloid tissues and fibroblasts. miR-4417 up-regulation led to the suppression of proliferation, migration, and invasion, while induced cell apoptosis in keloid fibroblasts. However, miR-4417 depletion exerted an opposite effect. CyclinD1 harbored the binding sites with miR-4417. Besides, the expression of CyclinD1 was evidently decreased in keloid tissues and fibroblasts. Meanwhile, miR-4417 was negatively correlated with CyclinD1 in keloid tissue. The effect of CyclinD1 knockdown on keloid fibroblasts was similar to that of miR-4417 overexpression. Furthermore, the elevated of CyclinD1 expression rescued the effect of miR-4417 up-regulation on keloid fibroblasts. miR-4417/CyclinD1 axis was required for cell proliferation, apoptosis, migration, and invasion in keloid fibroblasts. In conclusion, miR-4417 and CyclinD1 may be potential therapeutic targets for the treatment of keloid.

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Authors and Affiliations

  1. Department of Plastic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Pei Liu, Lin Xia, Min Du & Zhensheng Hu

  2. Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Yaotian Hu

Authors
  1. Pei Liu
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  2. Yaotian Hu
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  3. Lin Xia
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  4. Min Du
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  5. Zhensheng Hu
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Correspondence to Zhensheng Hu.

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Communicated by Kundan Sengupta

Corresponding editor: Kundan Sengupta

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Liu, P., Hu, Y., Xia, L. et al. miR-4417 suppresses keloid fibrosis growth by inhibiting CyclinD1. J Biosci 45, 47 (2020). https://doi.org/10.1007/s12038-020-0018-9

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  • DOI: https://doi.org/10.1007/s12038-020-0018-9

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