PRL-3 Promotes Growth And Metastasis Of Osteosarcoma And Its Molecular Mechanism

Osteosarcoma is one of the most frequently diagnosed primary bone tumors,which accounts for 5% of childhood and adolescent cancers.Studies have shown that the malignant phenotypes of osteosarcoma such as excessive proliferation,metastasis,especially lung metastasis,and resistance to chemotherapy are the major causes of high recurrence and mortality of osteosarcoma.Thus,exploring the key molecules involved in the malignant biological behavior of osteosarcoma and its regulatory mechanisms,will not only help us to clarify the pathogenesis of osteosarcoma,but also provide candidate targets for the clinical diagnosis and treatment of osteosarcoma.PRL-3(Phosphatase of Regenerating Liver-3)is an important member of protein tyrosine phosphatase family.Accumulating evidences demonstrate that PRL-3 is upregulated in many types of tumor tissues and cells,and exerts an important role in malignant biology behaviors of tumors like dysregulated proliferation,migration and invasion.We have previously found that PRL-3 was significantly upregulated in osteosarcoma tissues.Besides,we also found that PRL-3 was expressed at higherlevels in osteosarcoma cell lines with high metastatic capacity but not with low-metastatic cell lines.These results indicated that PRL-3 may paly a critical role in the tumorigenesis and progress of osteosarcoma.miR-103 a is an important microRNA screened by us with miRNA microarray.We have identified previously that PRL-3 negatively regulates miR-103 a in osteosarcoma.Many studies have indicated that miR-103 a widely participates in tumor cells' malignant behaviors in various cancers like colorectal cancer,hepatocellular cancer and glioblastoma.However,whether and how miR-103 a affects osteosarcoma remains to be explored.In the present project,we want to explore the following scientific issues.1.What's role does PRL-3 paly in the tumorigenesis and progression of osteosarcoma? 2.What's the detailed mechanism by which PRL-3 regualtes the tumorigenesis and progression of osteosarcoma?In order to solve the above scientific problems,we conducted the following four tasks: 1.To analyze PRL-3 expression in patients with osteosarcoma and evaluate the association between PRL-3 and osteosarcoma growth and metastasis.2.To investigate the effects of PRL-3 on the proliferation,migration and invasion of osteosarcoma cells in vitro.3.To confirm the effects of PRL-3 on the growth and metastasis of osteosarcoma in tumor-bearing animal model.4.To clarify the molecular mechanism of PRL-3 in promoting the growth and metastasis of osteosarcoma.Our results showed that: 1.PRL-3 is upregulated in osteosarcoma tissues as compared with that in normal bone tissue,and overexpression of PRL-3 is closely correlated with poor outcome of osteosarcoma patients.2.PRL-3 is upregulated in osteosarcoma cell lines and promotes osteosarcoma cells proliferation,migration and invasion.3.PRL-3 promotes growth and metastasis of osteosarcoma in vivo.4.PRL-3exerts its function in osteosarcoma through negatively regulating miR-103 a.In summary,we concluded that PRL-3 promotes growth and metastasis of osteosarcoma by negatively regulating miR-103 a expression.Our data not only enriche the understanding of the occurrence and development of osteosarcoma,butalso provide new theoretical basis for PRL-3 as a potential target for diagnosis and treatment of osteosarcoma.