MiR-106b regulates the proliferation and differentiation of neural stem/progenitor cells through Tp53inp1-Tp53-Cdkn1a axis

Xiaohuan Xia, Hongfang Lu, Chunhong Li, Yunlong Huang, Yi Wang, Xiaoyu Yang, Jialin C. Zheng

Research output: Contribution to journalArticle

Abstract

Background: Recent studies suggested that miR-17~106 family was involved in the regulation of neural stem/progenitor cells (NPCs). However, distinct function of each family member was reported in regulating stem cells within and without the brain. Hence, to investigate the roles of individual miRNAs in miR-17~106 family and mechanisms underlying their effects on neurogenesis is important to extend our understanding in the CNS development. Methods: Here, we examined the influence of miR-106a/b on the proliferation, differentiation, and survival of embryonic NPCs using specific mimics and inhibitor. The targets of miR-106a/b were identified from miRNA target prediction database and confirmed by luciferase assay. Specific siRNAs were utilized to erase the effects of miR-106a/b on the expression levels of target genes. Results: A positive correlation was observed between the temporal reduction of miR-106a/b expression levels and the decline of NPC pools in vivo and in vitro. The perturbation of miR-106's function approaches revealed that miR-106b, but not miR-106a, facilitated the maintenance of NPCs and repressed the generation of both neuronal and glial cells, without preference to a particular lineage. No effect was observed for miR-106a/b in NPCs' survival. The influence of miR-106b on NPCs' proliferation and differentiation is likely achieved by directly inhibiting the expression of Tp53inp1 and Cdkn1a, key components of Tp53inp1-Tp53-Cdkn1a axis. Conclusion: Our study demonstrated a novel axis, miR-106b-Tp53inp1-Tp53-Cdkn1a, in regulating the proliferation and differentiation of NPCs.

Original languageEnglish (US)
Article number282
JournalStem Cell Research and Therapy
Volume10
Issue number1
DOIs
StatePublished - Sep 23 2019

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Neural Stem Cells
Stem cells
Stem Cells
MicroRNAs
Neurogenesis
Cell proliferation
Embryonic Stem Cells
Luciferases
Neuroglia
Cell Differentiation
Assays
Brain
Cell Survival
Genes
Maintenance
Cell Proliferation
Databases

Keywords

  • Cdkn1a
  • Differentiation
  • Neural stem/progenitor cells
  • Proliferation
  • Tp53inp1
  • miR-106

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Cite this

MiR-106b regulates the proliferation and differentiation of neural stem/progenitor cells through Tp53inp1-Tp53-Cdkn1a axis. / Xia, Xiaohuan; Lu, Hongfang; Li, Chunhong; Huang, Yunlong; Wang, Yi; Yang, Xiaoyu; Zheng, Jialin C.

In: Stem Cell Research and Therapy, Vol. 10, No. 1, 282, 23.09.2019.

Research output: Contribution to journalArticle

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title = "MiR-106b regulates the proliferation and differentiation of neural stem/progenitor cells through Tp53inp1-Tp53-Cdkn1a axis",
abstract = "Background: Recent studies suggested that miR-17~106 family was involved in the regulation of neural stem/progenitor cells (NPCs). However, distinct function of each family member was reported in regulating stem cells within and without the brain. Hence, to investigate the roles of individual miRNAs in miR-17~106 family and mechanisms underlying their effects on neurogenesis is important to extend our understanding in the CNS development. Methods: Here, we examined the influence of miR-106a/b on the proliferation, differentiation, and survival of embryonic NPCs using specific mimics and inhibitor. The targets of miR-106a/b were identified from miRNA target prediction database and confirmed by luciferase assay. Specific siRNAs were utilized to erase the effects of miR-106a/b on the expression levels of target genes. Results: A positive correlation was observed between the temporal reduction of miR-106a/b expression levels and the decline of NPC pools in vivo and in vitro. The perturbation of miR-106's function approaches revealed that miR-106b, but not miR-106a, facilitated the maintenance of NPCs and repressed the generation of both neuronal and glial cells, without preference to a particular lineage. No effect was observed for miR-106a/b in NPCs' survival. The influence of miR-106b on NPCs' proliferation and differentiation is likely achieved by directly inhibiting the expression of Tp53inp1 and Cdkn1a, key components of Tp53inp1-Tp53-Cdkn1a axis. Conclusion: Our study demonstrated a novel axis, miR-106b-Tp53inp1-Tp53-Cdkn1a, in regulating the proliferation and differentiation of NPCs.",
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T1 - MiR-106b regulates the proliferation and differentiation of neural stem/progenitor cells through Tp53inp1-Tp53-Cdkn1a axis

AU - Xia, Xiaohuan

AU - Lu, Hongfang

AU - Li, Chunhong

AU - Huang, Yunlong

AU - Wang, Yi

AU - Yang, Xiaoyu

AU - Zheng, Jialin C.

PY - 2019/9/23

Y1 - 2019/9/23

N2 - Background: Recent studies suggested that miR-17~106 family was involved in the regulation of neural stem/progenitor cells (NPCs). However, distinct function of each family member was reported in regulating stem cells within and without the brain. Hence, to investigate the roles of individual miRNAs in miR-17~106 family and mechanisms underlying their effects on neurogenesis is important to extend our understanding in the CNS development. Methods: Here, we examined the influence of miR-106a/b on the proliferation, differentiation, and survival of embryonic NPCs using specific mimics and inhibitor. The targets of miR-106a/b were identified from miRNA target prediction database and confirmed by luciferase assay. Specific siRNAs were utilized to erase the effects of miR-106a/b on the expression levels of target genes. Results: A positive correlation was observed between the temporal reduction of miR-106a/b expression levels and the decline of NPC pools in vivo and in vitro. The perturbation of miR-106's function approaches revealed that miR-106b, but not miR-106a, facilitated the maintenance of NPCs and repressed the generation of both neuronal and glial cells, without preference to a particular lineage. No effect was observed for miR-106a/b in NPCs' survival. The influence of miR-106b on NPCs' proliferation and differentiation is likely achieved by directly inhibiting the expression of Tp53inp1 and Cdkn1a, key components of Tp53inp1-Tp53-Cdkn1a axis. Conclusion: Our study demonstrated a novel axis, miR-106b-Tp53inp1-Tp53-Cdkn1a, in regulating the proliferation and differentiation of NPCs.

AB - Background: Recent studies suggested that miR-17~106 family was involved in the regulation of neural stem/progenitor cells (NPCs). However, distinct function of each family member was reported in regulating stem cells within and without the brain. Hence, to investigate the roles of individual miRNAs in miR-17~106 family and mechanisms underlying their effects on neurogenesis is important to extend our understanding in the CNS development. Methods: Here, we examined the influence of miR-106a/b on the proliferation, differentiation, and survival of embryonic NPCs using specific mimics and inhibitor. The targets of miR-106a/b were identified from miRNA target prediction database and confirmed by luciferase assay. Specific siRNAs were utilized to erase the effects of miR-106a/b on the expression levels of target genes. Results: A positive correlation was observed between the temporal reduction of miR-106a/b expression levels and the decline of NPC pools in vivo and in vitro. The perturbation of miR-106's function approaches revealed that miR-106b, but not miR-106a, facilitated the maintenance of NPCs and repressed the generation of both neuronal and glial cells, without preference to a particular lineage. No effect was observed for miR-106a/b in NPCs' survival. The influence of miR-106b on NPCs' proliferation and differentiation is likely achieved by directly inhibiting the expression of Tp53inp1 and Cdkn1a, key components of Tp53inp1-Tp53-Cdkn1a axis. Conclusion: Our study demonstrated a novel axis, miR-106b-Tp53inp1-Tp53-Cdkn1a, in regulating the proliferation and differentiation of NPCs.

KW - Cdkn1a

KW - Differentiation

KW - Neural stem/progenitor cells

KW - Proliferation

KW - Tp53inp1

KW - miR-106

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