MicroRNA‑150 functions as a tumor suppressor and sensitizes osteosarcoma to doxorubicin‑induced apoptosis by targeting RUNX2

Abstract

Osteosarcoma (OS) is the most common form of bone malignancy in children and adolescents. MicroRNAs (miRNAs) have been associated with the development and progression of OS. In the present study, reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8, luciferase and Transwell assays were performed to investigate the biological function of microRNA-150 (miR-150) in OS. The results revealed that miR-150 was significantly downregulated in OS cell lines (HOS, SAOS2, MG-63 and U2OS) in comparison with the normal osteoblast cells (hFOB1.19). Overexpression of miR-150 significantly inhibited cell proliferation in OS cells. miR-150 could sensitize OS cells to chemotherapy treatment of doxorubicin. Runt-related transcription factor 2 (RUNX2) was identified as a target gene of miR-150. RUNX2 knockdown exhibited similar inhibitory effects on both OS cell proliferation and chemotherapy sensitivity. Restoration of RUNX2 reversed the biological function of miR-150. Finally, miR-150 overexpression and RUNX2 knockdown enhanced caspase-3 cleavage. Taken together, the present study established a novel molecular mechanism, in that miR-150 plays tumor suppressor and chemoprotective roles by targeting RUNX2 in OS, indicating that miR-150 may be a potential therapeutic target for OS therapy in the future.

Decreased MicroRNA-150 Exacerbates Neuronal Apoptosis in the Diabetic Retina

“…Inhibition of miR-150 is known to promote apoptosis [ 20 , 39 ], while overexpressing miR-150 can reduce the apoptosis of cells under hypoxia/ischemia conditions [ 21 , 40 ]. However, some cancer or endothelial cells with miR-150 overexpression have increased apoptosis under different treatments [ 41 , 42 ]. Thus, the function of miR-150 in regulating apoptosis might be tissue-specific and treatment-dependent, which might also be associated with its direct downstream targets.…”

RUNX2 as a promising therapeutic target for malignant tumors

“…In details, the results of luciferase reporter assay demonstrated that RUNX2 is a direct target of miR-150 and miR-150-RUNX2 axis affects the chemical sensitivity of osteosarcoma cells by regulating the expression levels of apoptosis proteins such as increasing the expression levels of cleaved caspase-3 and cleaved caspase-8 while reducing the expression levels of cleaved caspase-3 and cleaved caspase-8. 27 With the deepening of research, the regulatory signaling pathways, potential targets and corresponding drugs related to RUNX2 are emerging research hotspot against osteosarcoma. 35–37 …”

Immune classification of osteosarcoma

“…In our results, cluster 2 has the lowest amount of gene expression level of immunoregulatory cytokines TNF- α , IFN- γ , and IL1- β ( Figure 5 ) so that tumors in this cluster might be treated with bacterial vaccine. Otherwise, targeting RUNX2 oncogene with chemotherapy is suggested as a new therapeutic approach to osteosarcoma patients in recent studies [ 46 , 67 ] and cluster 2 has the highest amount of RUNX2 gene expression values compared to other clusters ( Figure 5A7 – B7 ) so with the help of further studies, tumors similar to those in cluster 2 also might be good candidates to treat with targeting RUNX2 in conjunction to standard chemotherapy.…”