Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3.
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Insulin-Like Growth Factor Binding Protein 3
/ genetics
Male
MicroRNAs
/ genetics
Middle Aged
Nasopharyngeal Carcinoma
/ genetics
Neoplasm Invasiveness
Neoplasm Metastasis
RNA, Circular
/ genetics
Up-Regulation
/ genetics
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
23 07 2020
23 07 2020
Historique:
received:
25
02
2020
accepted:
13
07
2020
revised:
08
07
2020
entrez:
25
7
2020
pubmed:
25
7
2020
medline:
26
3
2021
Statut:
epublish
Résumé
Accumulating evidences indicate that circular RNAs (circRNAs), a subclass of noncoding RNAs, play important role in regulating gene expression in eukaryotes. Hsa_circ_0046263 (circ-0046263) was found aberrantly expressed in nasopharyngeal carcinoma (NPC), but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, RNase R assay, and nucleic acid electrophoresis were conducted to verify the identification of circ-0046263. Nuclear separation and fluorescence in situ hybridization (FISH) assays were used to determine the localization of circ-004263. Dual luciferase reporter and RNA immunoprecipitation (RIP) were employed to confirm the binding of circ-0046263 with miR-133a-5p. Colony formation, proliferation, wound healing, transwell, western blot, and in vivo tumor growth and metastasis assays were performed to assess the roles of circ-0046263, miR-133a-5p, IGFBP3 and their interactions in NPC cells. Circ-0046263 was upregulated in both NPC cell lines and tissues. The in vitro functional studies revealed that knockdown of circ-0046263 inhibited the proliferation, invasion, and migration of NPC cells, whereas its overexpression produced the opposite result. In vivo experiments indicated that knockdown or overexpression of circ-0046263 attenuated or promoted tumor growth and metastasis, respectively. Mechanistically, circ-0046263 could act as a miRNA sponge to absorb miR-133a-5p and upregulate the expression of miRNA downstream target IGFBP3. In addition, miR-133a-5p inhibition or IGFBP3 overexpression could rescue the malignant behavior induced by circ-0046263 silencing. Finally, circ-0046263 plays a tumor-promoting role in NPC to enhance malignant behavior through the miR-133a-5p/IGFBP3 axis, which could be a potential target for NPC therapy.
Identifiants
pubmed: 32703944
doi: 10.1038/s41419-020-02785-3
pii: 10.1038/s41419-020-02785-3
pmc: PMC7378203
doi:
Substances chimiques
IGFBP3 protein, human
0
Insulin-Like Growth Factor Binding Protein 3
0
MIRN133 microRNA, human
0
MicroRNAs
0
RNA, Circular
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562Références
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