J Cancer 2020; 11(6):1351-1358. doi:10.7150/jca.33488
High level of RNF187 contributes to the progression and drug resistance of osteosarcoma
Department of Orthopedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
* The authors contributed equally to this study
Wan WB, Wu K, Peng K, Qiu ZQ, Duan ZB, Chen X, Xu ZM, Cheng K, Zhao JMH, Shi QM. High level of RNF187 contributes to the progression and drug resistance of osteosarcoma. J Cancer 2020; 11(6):1351-1358. doi:10.7150/jca.33488. Available from https://www.jcancer.org/v11p1351.htm
Objectives: Ring finger protein 187 (RNF187) was recently demonstrated to be up-regulation and function as a promoter in multiple cancers. However, the roles of RNF187 in osteosarcoma (OS) are unclear. Here, we tried to reveal the clinicopathological and biological roles of RNF187 in OS.
Materials and Methods: We employed the quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to determine the expression of RNF187 in OS tissues and cells. Migration and invasion capacities were analyzed by wound healing and transwell assays, and colony formation and CCK8 assays were performed to investigate proliferative ability. The functional effects of RNF187 on OS drugs resistance were further determined by CCK8 and western blot assays. Then, the relationship between RNF187 expression and clinical implications was analyzed by tissue microarrays (TMAs) including 51 OS cases. Moreover, the prognostic value was also determined by Kaplan-Meier analysis.
Results: We reported that RNF187 mRNA was significantly increased in OS tissues compared to matched nontumorous tissues (3.83 ±0.79 vs. 1.70 ± 0.63), which was in line with the IHC assay in TMAs. By RNA interference and cDNA transfection, we showed high level of RNF187 increased the migration, invasion and proliferation of OS cells. Moreover, we demonstrated that elevated RNF187 expression induced OS cell drugs resistance, activated the ERK1/2 molecular and markedly enhanced the BCL-2 expression. Clinically, OS patients with high level of RNF187 was associated with Histologic differentiation (p=0.001), an advanced Enneking stage (p=0.001), response to chemotherapy (p=0.004), and metastasis (p= 0.001). Clinically, our data displayed that the RNF187 overexpression in OS samples associated with shorten overall survival (p=0.001) and high tumor recurrence (p=0.001) in postoperative OS patients.
Conclusions: Our results indicate that Elevated RNF187 expression is a new adverse outcomes marker for OS patients and may be used as a new therapeutic target of OS.
Keywords: Osteosarcoma, RNF187, Drugs resistance, Prognosis