Overexpression of miR-669m inhibits erythroblast differentiation

Sci Rep. 2020 Aug 11;10(1):13554. doi: 10.1038/s41598-020-70442-y.

Abstract

MicroRNAs (miRNAs), one of small non-coding RNAs, regulate many cell functions through their post-transcriptionally downregulation of target genes. Accumulated studies have revealed that miRNAs are involved in hematopoiesis. In the present study, we investigated effects of miR-669m overexpression on hematopoiesis in mouse in vivo, and found that erythroid differentiation was inhibited by the overexpression. Our bioinformatic analyses showed that candidate targets of miR-669m which are involved in the erythropoiesis inhibition are A-kinase anchoring protein 7 (Akap7) and X-linked Kx blood group (Xk) genes. These two genes were predicted as targets of miR-669m by two different in silico methods and were upregulated in late erythroblasts in a public RNA-seq data, which was confirmed with qPCR. Further, miR-669m suppressed luciferase reporters for 3' untranslated regions of Akap7 and Xk genes, which supports these genes are direct targets of miR-669m. Physiologically, miR-669m was not expressed in the erythroblast. In conclusion, using miR-669m, we found Akap7 and Xk, which may be involved in erythroid differentiation, implying that manipulating these genes could be a therapeutic way for diseases associated with erythropoiesis dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism*
  • Amino Acid Transport Systems, Neutral / genetics
  • Amino Acid Transport Systems, Neutral / metabolism*
  • Animals
  • Cell Differentiation*
  • Erythroblasts / cytology*
  • Erythroblasts / metabolism
  • Erythropoiesis*
  • Female
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*

Substances

  • A Kinase Anchor Proteins
  • Akap7 protein, mouse
  • Amino Acid Transport Systems, Neutral
  • MicroRNAs
  • Xkh protein, mouse