MicroRNA-99 Family Targets AKT/mTOR Signaling Pathway in Dermal Wound Healing

Yi Jin, Stéphanie D. Tymen, Dan Chen, Zong Juan Fang, Yan Zhao, Dragan Dragas, Yang Dai, Phillip T. Marucha, Xiaofeng Zhou

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Recent studies suggest that microRNAs play important roles in dermal wound healing and microRNA deregulation has been linked with impaired wound repair. Here, using a mouse experimental wound healing model, we identified a panel of 63 differentially expressed microRNAs during dermal wound healing, including members of miR-99 family (miR-99a, miR-99b, miR-100). We further demonstrated that miR-99 family members regulate cell proliferation, cell migration, and AKT/mTOR signaling. Combined experimental and bioinformatics analyses revealed that miR-99 family members regulate AKT/mTOR signaling by targeting multiple genes, including known target genes (e.g., IGF1R, mTOR) and a new target (AKT1). The effects of miR-99 family members on the expression of IGF1R, mTOR and AKT1 were validated at both the mRNA and protein levels. Two adjacent miR-99 family targeting sites were identified in the 3′-UTR of the AKT1 mRNA. The direct interaction of miR-100 with these targeting sites was confirmed using luciferase reporter assays. The microRNA-100-directed recruitment of AKT1 mRNA to the RNAi-induced silencing complex (RISC) was confirmed by a ribonucleoprotein-IP assay. In summary, we identified a panel of differentially expressed microRNAs which may play important roles in wound healing. We provide evidence that miR-99 family members contribute to wound healing by regulating the AKT/mTOR signaling.

Original languageEnglish (US)
Article numbere64434
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 28 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Jin, Y., Tymen, S. D., Chen, D., Fang, Z. J., Zhao, Y., Dragas, D., Dai, Y., Marucha, P. T., & Zhou, X. (2013). MicroRNA-99 Family Targets AKT/mTOR Signaling Pathway in Dermal Wound Healing. PloS one, 8(5), [e64434]. https://doi.org/10.1371/journal.pone.0064434