Affiliations: Department of Orthopedics, Shanghai Zhabei District Central Hospital, Shanghai, China
Correspondence:
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Corresponding author: Kai Huang, Department of Orthopedics, Shanghai Zhabei District Central Hospital, Zhonghuaxin Road Zhabei District, Shanghai 200070, China. E-mail:13817784210@163.com
Abstract: Chondrosarcomas are malignant cartilage-forming tumors from low-grade to
high-grade aggressive tumors characterized by metastasis. Cisplatin is an
effective DNA-damaging anti-tumor agent for the treatment against a wide
variety of solid tumors. However, chondrosarcomas are notorious for their
resistance to conventional chemo- and radio- therapies. In this study, we
report miR-23b acts as a tumor suppressor in chondrosarcoma. The expressions
of miR-23b are down-regulated in chondrosarcoma patient samples and cell
lines compared with adjacent normal tissues and human primary chondrocytes.
In addition, overexpression of miR-23b suppresses chondrosarcoma cell
proliferation. By comparison of the cisplatin resistant chondrosarcoma cells
and parental cells, we observed miR-23b was significantly down regulated in
cisplatin resistant cells. Moreover, we demonstrate here Src kinase is a
direct target of miR-23b in chondrosarcoma cells. Overexpression of miR-23b
suppresses Src-Akt pathway, leading to the sensitization of cisplatin
resistant chondrosarcoma cells to cisplatin. This chemo-sensitivity effect
by the miR-23b-mediated inhibition of Src-Akt pathway is verified with the
restoration of Src kinase in miR-23b-overespressing chondrosarcoma cells,
resulting in the acquirement of resistance to cisplatin. In summary, our
study reveals a novel role of miR-23b in cisplatin resistance in
chondrosarcoma and will contribute to the development of the
microRNA-targeted anti-cancer therapeutics.
Keywords: microRNA-23b, chondrosarcoma cells, cancer therapeutics, Src-Akt pathway
