The therapeutic value of the SphK1-targeting microRNA-3677 in human osteosarcoma cells.
Aging (Albany NY)
; 12(6): 5399-5410, 2020 03 23.
Article
in En
| MEDLINE
| ID: mdl-32203055
ABSTRACT
Sphingosine kinase 1 (SphK1) is a potential therapeutic target for human osteosarcoma (OS). SphK1-targeting microRNAs (miRNAs) could have important therapeutic value for OS. We discovered that micorRNA-3677 (miR-3677) is a SphK1-targeting miRNA, inhibiting OS cell progression. The results of RNA-Pull down assay confirmed direct binding between biotinylated-miR-3677 and SphK1 mRNA in primary human OS cells. In established and primary human OS cells forced overexpression of miR-3677, by a lentiviral construct, decreased SphK1 3'-UTR (untranslated region) activity and downregulated SphK1 expression. Both were however enhanced with miR-3677 inhibition in OS cells. Function studies demonstrated that OS cell growth, proliferation and migration were inhibited with miR-3677 overexpression, but augmented with miR-3677 inhibition. MiR-3677 overexpression-induced anti-OS cell activity was reversed with re-expression of the 3'-UTR-depleted SphK1. Additionally, in SphK1 knockout OS cells (by CRISPR/Cas9 strategy), altering miR-3677 expression failed to further alter cell functions. Finally, we show that miR-3677 expression was significantly downregulated in primary human OS tissues, correlating with SphK1 mRNA upregulation. We conclude that targeting SphK1 by miR-3677 inhibits human OS cell progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteosarcoma
/
Phosphotransferases (Alcohol Group Acceptor)
/
MicroRNAs
Limits:
Humans
Language:
En
Journal:
Aging (Albany NY)
Journal subject:
GERIATRIA
Year:
2020
Document type:
Article
Affiliation country:
China