Knockdown of RNF183 suppressed proliferation of lung adenocarcinoma cells via inactivating the STAT3 signaling pathway.

Proteins of the RNF183 (RING finger 183) family proteins have been reported to be of great importance in tumor the initiation and progression. However, the biological role and regulatory mechanism of RNF183 in non small cell lung cancer (NSCLC) development and progression are poorly defined. Hence, lung adenocarcinoma (LUAD) cell proliferation, cell apoptosis and cell cycle were measured using Cell Counting Kit-8 and flow cytometry analysis, respectively. The correlation between RNF183 and SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase) was measured using coimmunoprecipitation and ubiquitination analysis in vitro. Tumor growth of NSCLC cells in vivo was measured using the nude mouse xenograft model. In this study, we verify that elevated RNF183 expression in tumor tissues of LUAD, origin from the TCGA, GEPIA, TIMER, and UALCAN database. RNF183 regulates apoptosis and cell cycle in vitro and tumor growth in vivo by activating the STAT3 pathway through ubiquitination of SHP2, a negative feedback regulator of the STAT3 pathway. Taken together, our results demonstrate that RNF183 regulates proliferation, apoptosis, and cell cycle in LUAD cells via modulation of SHP2/STAT3 signaling, suggesting the potential for targeting the RNF183-SHP2/STAT3 pathway for use in LUAD treatment.