RNF115 promotes lung adenocarcinoma through Wnt/\u03b2-catenin pathway activation by mediating APC ubiquitination

Xiao-Ting Wu,Yu-Han Wang,Xi-Wen Yang,Xiao-Yue Cai,Yun Dong,Wen-Feng Lu,Qing Cui,Ya-Ning Zhou,Ming Zhang

doi:10.1186/s40170-021-00243-y

Abstract

BackgroundPatients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/β-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear.MethodsRNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression.ResultsWe demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/β-catenin pathway via ubiquitination of adenomatous polyposis coli (APC).ConclusionThe current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Highlights

Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis
Through qRTPCR (Fig. 1c) and western blotting analysis (Fig. 1d, e) based on paired tumorous and adjacent nontumorous tissue sections collected from 25 LUAD patients, we detected that RING finger protein 115 (RNF115) was significantly (P < 0.001) upregulated in the tumorous tissues in comparison with that in the neighboring non-tumorous tissues
We evaluated its activity in adenomatous polyposis coli (APC) ubiquitination by immunoprecipitation and immunoblotting, through which we found that RNF115 knockdown in H358 cells inhibited the cellular APC ubiquitination (Fig. 5e)

Summary

Introduction

Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The detailed network of which Wnt pathway triggers metabolism switching into dominant glycolysis is still under study, several common downstream signaling pathways were identified to be modulated by Wnt signaling pathway and associate with direct metabolic remodeling in tumorous cells, including NSCLC cells [13]. These include but are not limited to TCF/LEF, c-myc, and Akt-mTOR pathways [14]. Wnt signaling pathway is able to indirectly influence the cellular metabolic processes through regulating relevant oncogenes and rate-limiting enzymes [14]

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