Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma
Zheng Tian,1,* Bin Guo,2,* Mei Yu,3 Chong Wang,1 Haoshaqiang Zhang,4 Qingfu Liang,1 Kunli Jiang,1 Li Cao5
1Bone Neoplasms Department, First Affiliated Hospital of Xinjiang Medical University, 2Orthopedics Department, Central Hospital, 3Ophthalmology Department, First Affiliated Hospital of Xinjiang Medical University, 4Orthopedics Department, People's Hospital of Xinjiang Uygur Autonomous Region, 5Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
*These authors contributed equally to this work
Objective: Abnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma.
Materials and methods: Expression levels of miR-128 and PTEN messenger RNA in osteosarcoma and noncancerous bone tissues obtained from 100 patients with primary osteosarcoma were detected by quantitative real-time polymerase chain reaction.
Results: Expression levels of miR-128 and PTEN messenger RNA in osteosarcoma tissues were significantly higher and lower, respectively, than those in noncancerous bone tissues (both P<0.001). In addition, high miR-128 expression and low PTEN expression, alone (miR-128-high or PTEN-low) or combined (miR-128-high/PTEN-low), were all dramatically associated with poor response to chemotherapy and positive metastasis. More importantly, the associations of miR-128-high/PTEN-low expression with these clinicopathological parameters were more significant than miR-128-high or PTEN-low alone. Finally, miR-128 expression, PTEN expression, miR-128/PTEN expression, the response to chemotherapy and the metastatic status were all identified as independent prognostic factors for overall survival and disease-free survival.
Conclusion: These findings indicate for the first time that the deregulation of miR-128 and its target gene PTEN may be involved in the aggressive progression of human osteosarcoma. Notably, the upregulation of miR-128 cooperating with the downregulation of PTEN may confer an unfavorable prognosis in patients with this malignancy.
Keywords: osteosarcoma, microRNA-128, phosphatase and tensin homolog, clinicopathological parameter, prognosis
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