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2018 ; 15
(4
): 4113-4120
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MicroRNA-499a-5p inhibits osteosarcoma cell proliferation and differentiation by
targeting protein phosphatase 1D through protein kinase B/glycogen synthase
kinase 3? signaling
#MMPMID29556286
Liu J
; Huang L
; Su P
; Song T
; Zhang W
; Fan J
; Liu Y
Oncol Lett
2018[Apr]; 15
(4
): 4113-4120
PMID29556286
show ga
A number of studies have attempted to elucidate the association between mircoRNAs
(miRNAs/miRs) and cancer-associated processes. The aim of the present study was
to determine how miR-499a-5p intervenes in human osteosarcoma cell proliferation
and differentiation. The cancerous tissues and adjacent non-cancerous tissues of
62 patients with osteosarcoma (OS) were collected. miRNA microarray analysis
revealed that 29 miRNAs were upregulated while 26 were downregulated, among which
miR-499a-5p expression was the most decreased. Western blot analysis and reverse
transcription-quantitative polymerase chain reaction demonstrated that the mRNA
and protein expression of miR-499a-5p was lower, while that of protein
phosphatase 1D (PPM1D) was higher in OS tissues compared with expression levels
in normal tissues. Furthermore, miR-499a-5p expression was markedly decreased in
the metastatic tumors and in those at stage III+IV compared with the
non-metastatic tumors and those at stage I, respectively. In addition, following
transfection of the human OS MG-63 cell line with an miR-499a-5p mimic, the
expression of miR-499a-5p was elevated while the protein and mRNA expression of
PPM1D was decreased. When combining these findings with the information obtained
from the Targetscan predictive software, it was confirmed that PPM1D was targeted
by miR-499a-5p. In MG-63 cells transfected with an miR-499a-5p mimic,
PPM1D-associated downstream proteins phosphorylated protein kinase B (p-Akt) and
phosphorylated glycogen synthase kinase 3? (p-GSK-3?) were significantly
downregulated compared with the negative control (NC) group, while the expression
of p-Akt and p-GSK-3? were significantly elevated in the tumor tissues compared
with the adjacent non-tumor tissues. Simultaneously, the growth and proliferation
activity of MG-63 cells were notably reduced when transfected with the
miR-499a-5p mimic, compared with the NC group. Therefore, it may be concluded
that miR-499a-5p suppresses OS cell proliferation and differentiation by
targeting PPM1D through modulation of Akt/GSK-3? signaling.