MicroRNA-33b Suppresses Migration and Invasion by Targeting c-Myc in Osteosarcoma Cells

MicroRNAs have emerged as fundamental regulators in gene expression through silencing gene expression at the post-transcriptional and translational levels. Osteosarcoma is the most common type of primary malignant bone tumor and is characterized by complex genetic changes and resistance to conventional treatments. In our study, the role of miR-33b in the progression and metastasis of osteosarcoma was investigated. Our results showed that miR-33b was significantly downregulated in osteosarcoma tissue and cell lines. Overexpression of miR-33b significantly inhibited cell proliferation, migration, and invasion in the MG-63 osteosarcoma cell line. Moreover, we also showed that c-Myc was negatively regulated by miR-33b at the posttranscriptional level, via a specific target site within the 3′UTR. Overexpression of c-Myc impaired miR-33b-induced inhibition of proliferation and invasion in osteosarcoma cells. The expression of c-Myc was frequently downregulated in osteosarcoma tumors and cell lines and was inversely correlated with miR-33b expression. Thus, our findings suggest that miR-33b inhibits osteosarcoma cells migration and invasion by targeting the c-Myc gene, acting as tumor suppressor. The findings of this study contribute to current understanding of the functions of miR-33b in osteosarcoma.

微小核糖核酸（MicroRNAs）已被证实为基因表达的核心调控因子，可通过在转录后及翻译水平沉默基因表达发挥调控作用。骨肉瘤（Osteosarcoma）是最为常见的原发性恶性骨肿瘤，其特征为复杂的遗传改变及对常规治疗的耐药性。本研究探讨了miR-33b在骨肉瘤进展与转移中的作用。研究结果显示，miR-33b在骨肉瘤组织及细胞系中显著下调。在MG-63骨肉瘤细胞系中，过表达miR-33b可显著抑制细胞增殖、迁移及侵袭能力。此外，本研究还证实，miR-33b可通过结合c-Myc基因3'非翻译区（3′UTR）内的特异性靶位点，在转录后水平负向调控c-Myc的表达。过表达c-Myc可削弱miR-33b对骨肉瘤细胞增殖与侵袭的抑制作用。在骨肉瘤肿瘤组织及细胞系中，c-Myc的表达通常呈下调状态，且与miR-33b的表达呈负相关。综上，本研究结果表明，miR-33b可通过靶向c-Myc基因抑制骨肉瘤细胞的迁移与侵袭，发挥肿瘤抑制因子的作用。本研究的发现加深了学界对miR-33b在骨肉瘤中功能的现有认知。