High Levels Of E3 Ubiquitin Ligase RNF128 Promote The Progression Of Non-small Cell Lung Cancer

Objectives:Ring finger protein 128?RNF128?is a member of the E3 ubiquitin ligase family.Previous studies have focused on its effects on immunological effect T-cell function,which has been shown to play a key role in balancing peripheral immune tolerance and autoimmune diseases.Recent research suggested that the abnormal expression of RNF128 might be involved in tumorigenesis.So far,its impact on non-small cell lung cancer and its potential mechanisms remains unclear.The main purpose of this study was to investigate the expression of RNF128 in NSCLC and its prognosis,and to explore its mechanism to promote the progression of NSCLC.Materials and Methods:The expression levels of RNF128 RNA and protein in NSCLC tissues and corresponding adjacent tissues were determined by immunohistochemistry,real-time PCR and Western blot.208 cases of non-small cell lung cancer tissue microarrays?TMAs?were used to evaluate the expression of RNF128,and the relationship between RNF128 expression and clinicopathological features and prognosis was analyzed by clinical pathology and patient follow-up data.The expression of RNF128was regulated to investigate the relationship between its expression and invasion,migration,colony formation and proliferation of NSCLC cells.Transwell experiments and wound healing experiments were used to assess the invasiveness of cells.Results:The expression of RNF128 mRNA in NSCLC tissues was higher than that in adjacent tissues?2.60±1.25 vs.0.50±0.02?.The expression of RNF128 protein in NSCLC tissues was also higher than that in adjacent tissues?6.25±0.99 vs.3.77±0.55?.Immunohistochemistry showed that the expression of RNF128 in tissue microarray showed that the expression heterogeneity of RNF128 in NSCLC tissues was obvious,and the expression of RNF128 in most cancer tissues was higher than that in adjacent tissues.According to the ratio of RNF128 immunostaining intensity to positive cells,NSCLC tissues were divided into RNF128 low expression group?52%,108/208?and RNF128 high expression group?48%,100/208?.Combined with the clinicopathological features of patients,the expression of RNF128 was significantly correlated with the malignant clinicopathological features of NSCLC,such as lymph node metastasis(P=1.16×10^-4)and advanced tumor?P=0.012?.Combined with prognostic analysis,the OS of RNF128 high expression group was significantly lower than that of RNF128 low expression group(34.1%vs.65.9%,P=1.5×10^-5).Univariate analysis showed that poor differentiation,lymph node metastasis,advanced TNM stage,and RNF128 overexpression were significant indicators of poor OS in non-small cell lung cancer.In multivariate analysis,RNF128expression?HR,1.658;95%CI,1.131-2.432;P=0.01?remained significantly associated with 5-year OS.After cell interference with RNF128 expression,cell invasion,migration,colony formation and proliferation were significantly inhibited.Conclusions:High expression of RNF128 promotes invasion and metastasis of NSCLC,and its expression may be a new prognostic indicator and potential therapeutic target for NSCLC.