LncRNA MIR4435-2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR-1224-5p/TGFBR2 axis.
Animals
Base Sequence
Brain Neoplasms
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioblastoma
/ genetics
Humans
Male
Mice, Inbred BALB C
MicroRNAs
/ genetics
Neoplasm Invasiveness
RNA, Long Noncoding
/ genetics
RNA, Messenger
/ genetics
Receptor, Transforming Growth Factor-beta Type II
/ metabolism
Signal Transduction
/ genetics
Up-Regulation
/ genetics
MIR4435-2HG
TGFBR2
glioblastoma
miR-1224-5p
proliferation and invasion
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
01
08
2019
revised:
29
11
2019
accepted:
23
12
2019
pubmed:
23
4
2020
medline:
29
4
2021
entrez:
23
4
2020
Statut:
ppublish
Résumé
Glioblastoma (GBM) belongs to the high-grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non-coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435-2 Host Gene (MIR4435-2HG) in GBM. Data from GEPIA database showed that MIR4435-2HG was up-regulated in GBM tissues and high expression of MIR4435-2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up-regulation of MIR4435-2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435-2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435-2HG overexpression driven GBM progression. Furthermore, MIR44435-2HG was found to sponge miR-1224-5p and suppress miR-1224-5p expression; overexpression of miR-1224-5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435-2HG overexpression. In a subsequent study, miR-1224-5p was found to target transforming growth factor-beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR-1224-5p exerted tumour-suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper-proliferation and invasion of GBM cells with MIR4435-2HG overexpression. Clinically, the down-regulation of miR-1224-5p and up-regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435-2HG in GBM and underlies the key function of MIR4435-2HG-driven GBM progression via targeting miR-1224-5p/TGFBR2 axis.
Identifiants
pubmed: 32319715
doi: 10.1111/jcmm.15280
pmc: PMC7294147
doi:
Substances chimiques
MIRN1224 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
RNA, Messenger
0
Receptor, Transforming Growth Factor-beta Type II
EC 2.7.11.30
TGFBR2 protein, human
EC 2.7.11.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6362-6372Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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