LINC00266-1/miR-548c-3p/SMAD2 feedback loop stimulates the development of osteosarcoma.
Animals
Apoptosis
/ genetics
Carcinogenesis
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Feedback, Physiological
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Neoplasm Metastasis
Osteoclasts
/ metabolism
Osteosarcoma
/ genetics
Phenotype
Prognosis
Promoter Regions, Genetic
/ genetics
RNA, Long Noncoding
/ genetics
Smad2 Protein
/ metabolism
Transcription, Genetic
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:
24 07 2020
24 07 2020
Historique:
received:
26
11
2019
accepted:
09
07
2020
revised:
04
07
2020
entrez:
26
7
2020
pubmed:
28
7
2020
medline:
27
3
2021
Statut:
epublish
Résumé
Osteosarcoma (OS) is one of the most common primary bone malignancies and accounts for 3.4% of pediatric tumors. Its 5-year survival is as low as about 20%. Differentially expressed lncRNAs in OS profiling were searched in the downloaded profile of GSE12865. As a result, LINC00266-1 was detected to be upregulated in both GSE12865 and OS tissues we collected. SMAD2 was the downstream target binding to promoter sites of LINC00266-1, displaying a positive regulatory interaction. Knockdown of LINC00266-1 suppressed the proliferative and metastatic abilities, and promoted the apoptosis in OS cells. Besides, knockdown of LINC00266-1 significantly alleviated the growth of OS in vivo. MiR-548c-3p was the sponge miRNA of LINC00266-1, which was able to reverse the regulatory effects of LINC00266-1 on OS cell phenotypes. Moreover, miR-548c-3p bound to the 3'-UTR of SMAD2 and thus downregulated SMAD2. Overexpression of SMAD2 partially reversed the regulatory effects of LINC00266-1 on OS cell phenotypes. Finally, we have identified that LINC00266-1/miR-548c-3p/SMAD2 feedback loop was responsible for stimulating the development of OS.
Identifiants
pubmed: 32709857
doi: 10.1038/s41419-020-02764-8
pii: 10.1038/s41419-020-02764-8
pmc: PMC7381647
doi:
Substances chimiques
MIRN548 microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
SMAD2 protein, human
0
Smad2 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
576Références
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