LncRNA HOXA11-AS aggravates the keloid formation by targeting miR-148b-3p/IGFBP5 axis

Biochem Biophys Res Commun. 2021 Dec 3:581:60-67. doi: 10.1016/j.bbrc.2021.09.074. Epub 2021 Oct 4.

Abstract

Long non-coding RNA (lncRNA) homeobox (HOX) A11 antisense (HOXA11-AS) mediates cell-biological phenotypes of keloid fibroblasts and influence the keloid progression, yet the underlying mechanism need to be further understood. HOXA11-AS, microRNA miR-148b-3p and Insulin like growth factor binding protein 5 (IGFBP5) expression were detected by RT-qPCR or western blot. CCK-8 and colony formation assays were applied to examine the cell proliferation. The cell migration was determined via Transwell migration assays. The cell apoptosis was determined by western blots with anti-Bax antibodies and anti-Cleaved Caspase-3 antibodies. The interplay between miR-148b-3p, HOXA11-AS and IGFBP5 was confirmed by luciferase reporter or RNA immunoprecipitation assay. The amplification of HOXA11-AS and IGFBP5 was detected in keloid and keloid fibroblasts, while miR-148b-3p expression was reduced. Moreover, downregulation of HOXA11-AS in keloid fibroblasts inhibited cell proliferation, migration and triggered apoptosis. Mechanically, HOXA11-AS was proved to sponge miR-148b-3p and abrogate the inhibition on miR-148b-3p target, IGFBP5 mRNA, thus promoting keloid fibroblasts proliferation, migration and inhibiting apoptosis. These results find that HOXA11-AS promotes keloid progression by miR-148b-3p/IGFBP5 axis, suggesting the potential of targeting HOXA11-AS/miR-148b-3p/IGFBP5 axis to combat keloid.

Keywords: Keloid; Keloid fibroblasts; LncRNA; Migration; Proliferation.

MeSH terms

  • Apoptosis / genetics
  • Case-Control Studies
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Movement
  • Cell Proliferation
  • Computational Biology / methods
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genes, Reporter
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Insulin-Like Growth Factor Binding Protein 5 / genetics*
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism
  • Keloid / genetics*
  • Keloid / metabolism
  • Keloid / pathology
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Skin / metabolism
  • Skin / pathology
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • HOXA11 protein, human
  • Homeodomain Proteins
  • IGFBP5 protein, human
  • Insulin-Like Growth Factor Binding Protein 5
  • MIRN148 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • bcl-2-Associated X Protein
  • Luciferases
  • CASP3 protein, human
  • Caspase 3