Our results suggest that miR-21 expression has a key role in regulating cellular processes in osteosarcoma, likely through regulating RECK and may serve as a therapeutic target.
The results showed that circulating levels of miR-21 were significantly higher in osteosarcoma patients than controls, while miR-199a-3p and miR-143 were decreased in osteosarcoma patients.
miR-21 might be a good candidate for a therapeutic target, and a potential biomarker for the prediction of chemotherapeutic sensitivity and prognosis in patients with osteosarcoma.
The miR-21 in osteosarcoma cells is a significant modulator of the anti-tumor effect of CDDP by regulating the expression of bcl-2, and the study reveals a novel mechanism of osteosarcoma drug resistance.
This inhibitory effect is associated with the suppression of the upstream kinase MEK1/2, and is mediated via the repression of miR-21-5p and the consequent up-regulation of the MEK/ERK antagonist SPRY2 in osteosarcoma cells.
In summary, our findings suggested that miR-21 played an active role in osteosarcoma and it could predict the occurrence and development of osteosarcoma.
The aim of the present study was to analyse the correlation between miR-21 expression level and clinicopathologic features, as well as to assess the prognostic significance of miR-21 in osteosarcoma.
The expression level of serum miR-21 in patients with osteosarcoma is closely related to the therapeutic effects of osteosarcoma, which can be used as one of the potential biomarkers and therapeutic targets for the diagnosis and prediction of osteosarcoma.
Finally, we investigated the regulatory mechanism of XIST acting as a competitive endogenous RNA (ceRNA) of miR-21-5p in OS progression and metastasis. lncRNA XIST was significantly downregulated in osteosarcoma tissues and osteosarcoma cells, and associated with recurrence and short overall survival in OS patients.
The results of our meta-analysis revealed that elevated levels of miR-21, miR-214, miR-29, miR-9 and miR-148a were associated with poor prognosis in osteosarcoma.
PP2A was a direct target of miR-21, which participated in the effects of ASBEL and miR-21 on the activation of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3β (PI3K/AKT/GSK3β) and mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion.
Human osteosarcoma MG-63 cells and osteoblast hFOB1.19 cells were used to compare the expression of miRNA-21 using reverse transcription-quantitative polymerase chain reaction analysis.
Serum miRNA-21 may be used to effectively diagnose osteosarcoma and predict the prognosis of the disease. miRNA-21 knockdown inhibited the proliferation of osteosarcoma and promoted the expression of PTEN and TGF-β1 proteins in the osteosarcoma cells.
The expression levels of miR-21, mirR-221, and miR-106a were significantly higher in 90.42%, 84.04%, and 92.55 % of the osteosarcoma samples compared to the adjacent normal tissues (<i>P</i><0.05), respectively.
Downregulation of lncRNA-NEF and upregulation of miRNA-21 distinguished patients with osteosarcoma from healthy controls. lncRNA-NEF overexpression mediated the inhibition of miRNA-21 expression in osteosarcoma cell lines, while miRNA-21 overexpression did not significantly affect the expression of lncRNA-NEF. lncRNA-NEF overexpression inhibited, while miRNA-21 overexpression promoted, migration and invasion of osteosarcoma cell lines <i>in vitro</i>. miRNA-21 overexpression partially compensated the inhibitory effects of lncRNA-NEF overexpression on osteosarcoma cell migration and invasion.