Abstract
As the most common malignant primary bone tumor in childhood, osteosarcoma (OS) maintains a high recurrence, despite the significant improvements in the overall survival rate of high-grade OS patients during the recent decades. Therefore, a novel therapy strategy is required for OS treatment. Recently, various microRNAs (miRNAs or miRs) have been confirmed as deregulated in OS, and the miR-155 dysregulation in OS has been discovered by the microarray analysis. In the present study, the regulation of miR-155 on the OS cell proliferation, migration and invasion on the MG-63 cells was explored in vitro. The miR-155 mimics were found to promote cell proliferation, colony formation, migration and invasion significantly, compared to the control miRNA. An miR-155 inhibitor was also used to evaluate whether miR-155 served as a therapeutic target for OS. The results demonstrated that the miR-155 inhibitor significantly reduced the proliferation, colony formation, migration and invasion of the MG-63 OS cells. Thus, the study confirmed the oncogenic regulation on the OS progression of miR-155, which could serve as a therapeutic target with an miR-155 inhibitor.
Highlights
Osteosarcoma (OS) accounts for ~2.5% of all malignancies in pediatric patients and ~ 20% of all primary bone cancers [1], with a morphological and malignant heterogeneity [2]
To confirm the promotion of miR‐155 to the OS cell proliferation, the miR‐155 expression level was manipulated in MG‐63 cells, via transfection with the miR‐155 mimic or inhibitor
The time‐dependent promoting or reducing effect in cell proliferation of the miR‐155 mimic or inhibitor was indicated under the condition of enhanced or reduced miR‐155 levels in the MG‐63 cells (P
Summary
Osteosarcoma (OS) accounts for ~2.5% of all malignancies in pediatric patients and ~ 20% of all primary bone cancers [1], with a morphological and malignant heterogeneity [2]. >30% of OS patients with localized disease eventually develop distant metastases, mostly to the lungs and bones [3], Key words: miR‐155 inhibitor, osteosarcoma, proliferation, migration even following chemotherapy and surgical treatment. The oncogenic miRNA, miR‐21, which is aberrantly overexpressed in numerous types of tumor and induces cancer cell growth, migration, invasion and metastasis [16,17], has been indicated to be significantly overexpressed in OS tissues and induces invasion and migration of the OS cell line, MG‐63, by negatively regulating the tumor suppressor gene, reversion‐inducing‐cysteine‐rich protein with kazal motifs [18]. The oncogenic miR‐93 induces proliferation and invasion in OS [19], whereas miR‐20a promotes OS metastasis by regulating Fas expression [20]. The tumor suppressive miRNAs, including miR‐199a‐3p [21], miR‐125b [22], miR‐143 [23], miR‐382 and miR‐134 [24], are significantly downregulated in OS cells and attenuate proliferation and inhibition of migration, reduce cell viability and induce apoptosis. miR‐155 is well identified as an oncogenic miRNA in leukemia [25,26] and breast cancer [14], contributing to tumorigenicity and progression
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