1. The second affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China, 710004
2. Department of Osteology, Xi'an Hong-Hui Hospital affiliated to medical college of Xi'an Jiaotong University, Xi'an, Shaanxi, China, 710054
3. Department of Orthopaedics, the third affiliated hospital of Zhejiang Chinese Medical University, Hangzhou, China, 310005
4. Departments of Cardiology, the Ninth affiliated hospital of medical college of Xi'an Jiaotong University, Xi'an, Shaanxi, China, 710054
5. Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA, 80045
* These authors contribute equally to this work.
Elevated expression of survivin is observed in a number of cancer types, including human osteosarcoma. Few studies have demonstrated that survivin expression levels can be considered an independent predictor of survival for human osteosarcoma patients. However, the underlying molecular mechanisms of survivin in the process of human osteosarcoma carcinogenesis remain unclear. In the current study, we evaluated the biological effects of survivin knockdown on osteosarcoma cell proliferation, colony formation rate, and sensitivity to the chemotherapeutic agent cisplatin. We found that two different osteosarcoma cell lines, U2OS and Saos-2, have relatively higher expression levels of survivin, and specific knockdown of survivin resulted in a number of effects, such as inhibition of cell proliferation, decreased colony formation rate, cell cycle arrest at G2/M phase, induction of apoptosis, and increased sensitivity to cisplatin. In addition, we identified two microRNAs, miR-34a and miR-203, that are aberrantly expressed in human osteosarcoma cells and specifically target survivin by inhibiting its expression, therefore repressing osteosarcoma cell maintenance and proliferation.
Keywords: Survivin, osteosarcoma, cell proliferation, apoptosis, cisplatin