MiR-361-3p promotes tumorigenesis of osteosarcoma cells via targeting ARID3A

Abstract

MiR-361-3p has been reported in several types of human cancer. However, the expression profile and biological functions of miR-361-3p in osteosarcoma remain uncovered. The expression profiles of miR-361-3p in osteosarcoma tissues and cell lines were evaluated using RT-qPCR. In 88 osteosarcoma patients, survival analysis was performed using Kaplan-Meier curves; while prognostic significance of miR-361-3p was analyzed using Cox regression analysis. The effects of miR-361-3p on cell proliferation, migration and invasion capacities were analyzed using CCK-8 and transwell assays. The target genes of miR-361-3p were assessed using luciferase reporter assay, RT-qPCR, Western blot and rescue experiments. Xenograft assay was conducted to test tumor growth ability. MiR-361-3p was found to be upregulated in human osteosarcoma tissues and cell lines. The expression of miR-361-3p was observed to be closely associated with TNM stage and lung metastasis. High expression of miR-361-3p was found to be capable of predicting poor clinical prognosis in osteosarcoma patients. Whilst overexpression of miR-361-3p was demonstrated to promote the proliferation, migration and invasion of osteosarcoma cells; knockdown of miR-361-3p was shown to exhibit an opposite inhibitory effect. Bioinformatics analysis and luciferase reporter assays confirmed that ARID3A is a direct target of miR-361-3p. Functional assays demonstrated that osteosarcoma cell proliferation, migration and invasion were promoted by miR-361-3p via negative regulation of ARID3A. Finally, overexpression of ARID3A was shown to partially reverse the tumor-promoting effect of miR-361-3p. Besides, in vivo assays revealed that miR-361-3p overexpression facilitated tumor growth in nude mice. In conclusion, this study indicates that miR-361-3p is a crucial prognostic biomarker of osteosarcoma, and that targeting of miR-361-3p/ARID3A axis may be a promising strategy in osteosarcoma therapy.

Keywords: ARID3A; Biomarker; Osteosarcoma; Prognosis; miR-361-3p.