Inhibition of miR-9 decreases osteosarcoma cell proliferation

Abstract

Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as in vitro models. Small interfering RNA against miR-9 and miR-9 mimics were used to study the function of miR-9 in these two cell lines. We determined the effect of miR-9 inhibition on cell proliferation, cell cycle, apoptosis, and the protein expression of different genes. Our results demonstrated that miR-9 knockdown in the human OS cell lines inhibits their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The western blot analysis showed that cadherin-1 (CDH1), matrix metalloproteinase 13 (MMP-13), forkhead box O3 (FOXO3a), Bcl-2-like protein 11 (BCL2L11), and β-catenin (CTNNB1) are involved in miR-9 signaling. Moreover, miR-9 mimics rescued the effects caused by the inhibition of miR-9 in the OS cell lines. Our findings suggest that miR-9 is important for mediating OS cell migration, invasion, metastasis, and apoptosis. Inhibition of miR-9 could be further explored as a therapeutic target to treat OS.

Role of vasodilator‑stimulated phosphoprotein in RANKL‑differentiated murine macrophage RAW264.7 cells: Modulation of NF‑κB, c‑Fos and NFATc1 transcription factors

“…no. SW3015; Beijing Solarbio Science & Technology Co., Ltd.) for 2 h at room temperature, and then visualized with enhanced chemiluminescence substrate (Pierce; Thermo Fisher Scientific, Inc.) as previously described ( 14 , 15 ). GAPDH was used as a reference protein and lamin was used as a reference for nuclear p65.…”

Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line

“…In relation to the presence of this miRNA in OS, Xu S. et al have found that miR-9 is upregulated in OS tissues compared to non-cancerous tissues, and that this overexpression can be correlated with the tumor size and the aggressive progression of OS [ 108 ]. Gang W. et al have demonstrated that the inhibition of miR-9 enhances OS cell apoptosis and inhibits their metastatic potential [ 109 ].…”

“…Maia D. et al have reported that the high expression levels of miR-296-5p mediate drug resistance and is correlated to tumor recurrence in early-stage laryngeal carcinoma [ 115 ]. Yoon A. et al have demonstrated that miR-296-5p is enriched in cancer cells and, by downregulation of the p53-p21 WAF1 pathway, contributes to tumorigenesis [ 109 ]. miR-654-5p has also recently been identified as an oncomir through Ras/MAPK signaling in oral squamous-cell carcinoma [ 111 ].…”

The impact of miR-9 in osteosarcoma

“…[ 21 ] In osteosarcoma, inhibition of miR-9 decreases the proliferation of tumor cells by targeting p16. [ 39 , 40 ] In addition, miR-9 was upregulated in spontaneous canine osteosarcoma and promoted the invasion and migration of osteosarcoma cells. [ 41 ] Meanwhile, miR-9 was an oncogene and promoted proliferation of osteosarcoma through targeting Grap2 and cyclin D interacting protein.…”