MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1
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Kang Han1,3,*, Xiang Chen2,*, Na Bian3,*, Baoan Ma3, Tongtao Yang3, Chengkui Cai3, QingYu Fan3, Yong Zhou3 and TingBao Zhao1
1 Department of Spinal Cord Injury, General Hospital of Jinan Military Area Command of Chinese PLA, Jinan, Shandong, People’s Republic of China
2 Department of Baylor College of Medicine, Houston, Texas, USA
3 Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China
* These authors contributed equally to this work
Yong Zhou, email:
TingBao Zhao, email:
Keywords: microRNA, miR-195, osteosarcoma, CCND1, metastatic
Received: January 01, 2015 Accepted: February 12, 2015 Published: March 12, 2015
Metastasis is a leading cause of mortality for osteosarcoma patients. The molecular pathological mechanism remains to be elucidated. In the previously study, we established two osteosarcoma cell lines with different metastatic potentials. Differential expressed genes and proteins regarding metastatic ability have been identified. MicroRNAs are important regulators in tumorigenesis and tumor progression. In this study, microRNA microarray was used to assess the differential expressed miRNAs level between these two cell lines. One of the top ranked miRNAs-miR-195 was identified highly expressing in lowly metastatic cells. It was showed that over-expression of miR-195 substantially inhibits migration and invasion of osteosarcoma cells in vitro and pulmonary metastasis formation in vivo. Meanwhile, CCND1 was identified as the target gene of miR-195 and further studied. More importantly, Using real-time PCR, we evaluated the expression of miR-195 and CCND1 in osteosarcoma samples from 107 frozen biopsy tissues and 99 formalin- or paraformalin-fixed, paraffin-embedded (FFPE) tissues. Results indicated lowly expressed miR-195 or highly CCND1 correlated with positive overall survival and their expression inverse relate to each other. In summary, our study suggests miR-195 function as a tumor metastasis suppressor gene by down-regulating CCND1 and can be used as a potential target in the treatment of osteosarcoma.
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