Knockdown of microRNA-203 reduces cisplatin chemo-sensitivity to osteosarcoma cell lines MG63 and U2OS in vitro by targeting RUNX2

Abstract

Clinical studies have reported that miRNAs abnormal expression are associated with the generation of cisplatin-resistant to osteosarcoma. Our previous research found that miR-203 is downregulated in osteosarcoma cells and overexpressed miR-203 exerts antitumor properties on osteosarcoma cells. However, the role and mechanism of miR-203 in regulating the sensitivity of cisplatin in osteosarcoma cells remains unclear. This study aimed to investigate the effects of miR-203 in cisplatin therapy for osteosarcoma cells in vitro and determined the underlying mechanism. In this study, we found that miR-203 was significantly upregulated in osteosarcoma cells after exposure to cisplatin. miR-203 knockdown reduced the sensitivity of osteosarcoma cells to cisplatin by suppressing cell apoptosis, cell cycle arrest, and inducing invasion. Meanwhile, we found that miR-203 knockdown reduces the therapeutic sensitivity of osteosarcoma cells by upregulating RUNX2. Moreover, we found that RUNX2 silencing sensitizes osteosarcoma cells to chemotherapy treatment of cisplatin. In summary, our findings demonstrated that miR-203 knockdown reduces cisplatin chemo-sensitivity to osteosarcoma cells in vitro by targeting RUNX2, and speculated that miR-203 may be a target for drug resistance of osteosarcoma to cisplatin.

Keywords:

• apoptosis
• cell cycle
• cisplatin
• miR-203
• osteosarcoma
• RUNX2

Acknowledgments

The authors are indebted to Dr. Chen Lv for his expert review of the manuscript and the faculty of the translational medicine laboratory of the First Affiliated Hospital of Wenzhou Medical University for supplying the laboratory to finish this study.

Disclosure statement

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

Additional information

Funding

This study was supported by the Natural Science Foundation of Zhejiang Province (LQ20H060003), Zhejiang Medical and Health Science and Technology Project (2020KY633) and the Technology Bureau Projects of Wenzhou City (Y20190276, Y20190393 and Y20190435).

Notes on contributors

Zhengxiang Huang

Zhengxiang Huang, Master Degree, also work in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly study on the pathogenesis of microRNA.

Lintuo Huang

Lintuo Huang, Master Degree, also work in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly study on drug therapy for osteosarcoma.

Lue Liu

Lue Liu, Master Degree, work in Department of Orthopedics, the Third Affiliated Hospital of Wenzhou Medical University and mainly engage in drug therapy and surgery of osteosarcoma.

Lu Wang

Lu Wang, Master Degree, work in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly study on the surgery of malignant bone tumor.

Wenjun Lin

Wenjun Lin, Master Degree, work in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly study on the surgery of malignant bone tumor.

Xiongbai Zhu

Xiongbai Zhu, Master Degree, work in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly study on osteoarthritis, femoral head necrosis, trauma orthopedics.

Wei Su

Wei Su, Bachelor Degree, Study in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly engage in the molecular mechanism of bone tumors in children.

Chen Lv

Chen Lv, Doctoral Degree, work in Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University and mainly study on the pathogenesis of bone tumors, osteoarthritis and osteoporosis.