Abstract
Osteosarcoma is the most frequent primary bone tumor affects adolescents and young adults. Recently, microRNAs (miRNAs) are short, non-coding and endogenous RNAs that played as important roles in the initiation and progression of tumors. In this study, we try to explore the biological function and expression of miR-610 in the osteosarcoma. We showed that miR-610 expression was downregulated in the osteosarcoma tissues and cell lines. Elevated expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cycle, invasion and EMT program. Moreover, overexpression of miR-610 increased sensitivity of MG-63 and U2OS cells to cisplatin. Twist1 was identified as a direct target gene of miR-610 in the osteosarcoma cell. Furthermore, we demonstrated that Twist1 was upregulated in the osteosarcoma tissues and cell lines. The expression of Twist1 was negatively associated with the expression of miR-610 expression in the osteosarcoma tissues. Ectopic expression of Twist1 inhibited the sensitivity of miR-610-overexpressing MG-63 cells to cisplatin. We also showed that overexpression of Twist1 increased the proliferation and invasion of miR-610-overexpressing MG-63 cells. These data indicated that ectopic expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cylce, invasion and increased the sensitivity of osteosarcoma cells to cisplatin through targeting the Twist1 expression.
Highlights
Osteosarcoma is the most frequent primary bone tumor affects adolescents and young adults, which is prone to early metastasis and frequently occurs in the long bones [1,2,3,4,5]
Twist1 was identified as a direct target gene of miR-610 in the osteosarcoma cell
We demonstrated that Twist1 was upregulated in the osteosarcoma tissues and cell lines
Summary
Osteosarcoma is the most frequent primary bone tumor affects adolescents and young adults, which is prone to early metastasis and frequently occurs in the long bones [1,2,3,4,5]. Despite the recently advancements including adjuvant chemotherapy, radiotherapy and wide tumor excision, the prognosis and 5 years survival rate of these patients remains poor [6,7,8,9]. Chemotherapeutic drugs such as cisplatin and doxorubicin are well used in osteosarcoma and 5-year survival rate has been increased from 20% to 70% [10, 11]. The molecular mechanisms about acquiring chemoresistance are still unknow [12,13,14]. It is urgent need to find these molecular mechanisms to explore therapeutic strategies. Mounting evidences demonstrated that miRNAs act crucial roles in the development of drug resistance in different cancers [30,31,32,33]
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