MicroRNA-1253 Suppresses Cell Proliferation Migration and Invasion of Osteosarcoma by Targeting MMP9

Abstract

Purpose: MicroRNAs play an important role in osteosarcoma (OS) development and progress. Although miR-1253 was considered as a tumor-inhibitor in some cancers, it’s function in the OS is not clear. Methods: In our study, we examined the expression of miR-1253 in OS cells and osteoblast cells using quantitative real-time PCR. The proliferation of OS cells was measured by BrdU assay, and we performed transwell to detect migration and invasion of OS cells. Meanwhile, EMT proteins were tested by western blot. We used Bioinformatics to predict the target genes of miR-1253 and found out Matrix metalloproteinases9 (MMP9) was one of that. The direct combination between miR-1253 and MMP9 was verified by double luciferase reporting experiment. Quantitative real-time PCR and western blot were used to detect the expression of MMP9. Results: We found that the expression level of miR-1253 in OS cells was significantly lower than that in osteoblast cells. Overexpression of miR-1253 could significantly inhibit OS cell proliferation, migration, invasion and EMT. And then, MMP9 was predicted as a downstream target of miR-1253 by Bioinformatics analysis. Further experiments showed that miR-1253 could reduce the protein level of MMP9 by directly binding to the 3’-UTR of MMP9. Afterward, we performed a rescue experiment, in which both MMP9 and miR-1253 were overexpressed. Compared with the groups overexpressed miR-1253 alone, cell proliferation, migration and invasion in co-overexpression groups were improved. Conclusions: In summary, these results suggested that miR-1253 down-regulated in OS cells, and could suppress the proliferation, migration and invasion of OS cells. Its molecular regulatory mechanism was that inhibits the expression of the downstream target gene MMP9 by directly binding, thus affect OS cell functions. Therefore, miR-1253 has the potential to become a biomarker and therapeutic target for OS therapy.

Profili dell’espressione di MMP-9 e EMMPRIN nella rinosinusite cronica con poliposi nasali

“…miR-29b-3p has been found to directly target MMP-9 mRNA and that miR29b3p expression is moderately positively correlated with the expression of MMP-9 in CRSwNPs 6 . Other miRNAs that directly or indirectly affect MMP-9 expression include let-7e 7 , miR-129, miR-335 8 , miR-211 9 , miR-491-5p 10 and miR-1253 11 . Moreover, novel classes of ncRNAs that can regulate gene expression are tRNA-derived fragments (tRFs) and long ncRNAs 12 , 13 , whose role in the pathogenesis of CRSwNP remains to be elucidated.…”

“…Other miRNAs that directly or indirectly affect MMP-9 expression include let-7e 7 , miR-129, miR-335 8 , miR-211 9 , miR-491-5p 10 and miR-1253 11 . Moreover, novel classes of ncRNAs that can regulate gene expression are tRNAderived fragments (tRFs) and long ncRNAs 12,13 , whose role in the pathogenesis of CRSwNP remains to be elucidated.…”