Up-regulated lncRNA5322 elevates MAPK1 to enhance proliferation of hair follicle stem cells as a ceRNA of microRNA-19b-3p

Cell Cycle. 2019 Jul;18(14):1588-1600. doi: 10.1080/15384101.2019.1624111. Epub 2019 Jun 15.

Abstract

Hair follicle stem cells (HFSCs), located in the bulge region of the follicle, maintain hair follicle growth and cycling. Long non-coding RNAs (lncRNAs), non-protein coding transcripts, are widely known to play critical roles in differentiation and proliferation of stem cells. Therefore, the current study aimed to explore the regulatory roles of lncRNA5322 in HFSCs proliferation and the underlying regulatory mechanisms. Initially, the expression patterns of lncRNA5322 and microRNA-19b-3p (miR-19b-3p) in HFSCs were detected. Subsequently, gain-and loss-of-functions analyses were conducted to explore the roles of lncRNA5322, miR-19b-3p and mitogen-activated protein kinase 1 (MAPK1) in cell proliferation, colony formation and apoptosis of HFSCs, with the expression of cyclin-dependent kinase (CDK)1 and CDK2 examined. Also, the interaction relationships among lncRNA5322, miR-19b-3p and MAPK1 were explored. Furthermore, a mouse model was established to detect the roles of lncRNA5322, miR-19b-3p, and MAPK1 in wound contraction and epidermal regeneration. Over-expressed lncRNA5322 was found to promote proliferation, colony formation ability but inhibit apoptosis of HFSCs, in addition to up-regulation of the expression of CDK1 and CDK2. LncRNA5322 was found to act as a ceRNA of miR-19b-3p which directly targeted MAPK1. Furthermore, up-regulation of lncRNA5322 enhanced wound contraction and epidermal regeneration in vivo by increasing the expression of MAPK1 through functioning as a ceRNA of miR-19b-3p. In summary, the results in this study suggested that lncRNA5322 serves as a ceRNA of miR-19b-3p to elevate the expression of MAPK1, ultimately promoting HFSCs proliferation, wound contraction and epidermal regeneration of mouse model.

Keywords: Hair follicle stem cells; epidermal regeneration; long non-coding RNA5322; microRNA-19b-3p; mitogen-activated protein kinase 1; proliferation; wound contraction.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • HEK293 Cells
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Stem Cells / metabolism*
  • Up-Regulation
  • Wound Healing / genetics

Substances

  • MIRN19 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Mitogen-Activated Protein Kinase 1