MicroRNA-30a suppresses self-renewal and tumorigenicity of glioma stem cells by blocking the NT5E-dependent Akt signaling pathway.
5'-Nucleotidase
/ genetics
Adult
Aged
Animals
Apoptosis
Biomarkers, Tumor
/ genetics
Brain Neoplasms
/ genetics
Cell Proliferation
Cell Self Renewal
Female
GPI-Linked Proteins
/ genetics
Gene Expression Regulation, Neoplastic
Glioma
/ genetics
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Middle Aged
Neoplastic Stem Cells
/ metabolism
Prognosis
Proto-Oncogene Proteins c-akt
/ genetics
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Young Adult
Akt signaling pathway
Ecto-5′-nucleotidase
colony-formation ability
glioma stem cells
microRNA-30a
orthotopic tumor growth
proliferation
self-renewal
sphere-formation ability
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
04
12
2018
revised:
10
09
2019
accepted:
23
09
2019
pubmed:
19
2
2020
medline:
20
1
2021
entrez:
19
2
2020
Statut:
ppublish
Résumé
Over the past decade, increasing researches have demonstrated the implication of microRNAs (miRNAs or miRs) in tumorigenicity of glioma stem cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. Herein, we aim to investigate the role of miR-30a in the proliferation and self-renewal of GSCs and the possible mechanism in relation to ecto-5'-nucleotidase (NT5E)-dependent Akt signaling pathway. RT-qPCR and Western blot analysis were performed to determine the expression of miR-30a and NT5E in glioma tissues and cell lines. GSCs were isolated from glioma cells and identified using flow cytometry. The relationship between miR-30a and NT5E was determined by dual-luciferase reporter gene assay. Gain- and loss-of-function experiments were performed to examine the effects of miR-30a and NT5E on sphere formation, colony formation, and proliferation of GSCs in vitro, as well as orthotopic tumor growth of GSCs in nude mice. Additionally, the Akt signaling pathway was blocked with an Akt inhibitor, LY294002, to investigate its involvement in the regulatory effect of miR30a. miR-30a was poorly expressed in glioma tissues and cell lines as well as GSCs. NT5E, highly expressed in GSCs, was identified as a target of miR-30a. In addition, miR-30a upregulation or NT5E silencing could reduce GSC sphere formation, clone formation, proliferation, and orthotopic tumor growth in nude mice. Moreover, miR-30a inhibited the activation of the Akt signaling pathway by targeting NT5E, and ultimately suppressing the self-renewal and orthotopic tumor growth of GSCs. Our results demonstrate that miR-30a targets NT5E to inhibit the Akt signaling pathway, by which could suppress the self-renewal and orthotopic tumor growth of GSCs. Those findings may provide theoretical basis of miR-30a as a therapeutic target to suppress the glioma progression.
Identifiants
pubmed: 32067282
doi: 10.1096/fj.201802629RR
doi:
Substances chimiques
Biomarkers, Tumor
0
GPI-Linked Proteins
0
MIRN30b microRNA, human
0
MicroRNAs
0
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
5'-Nucleotidase
EC 3.1.3.5
NT5E protein, human
EC 3.1.3.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5128-5143Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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