CARMA3 Represses Metastasis Suppressor NME2 to Promote Lung Cancer Stemness and Metastasis

Rationale: CARD-recruited membrane-associated protein 3 (CARMA3) is a novel scaffold protein that regulates nuclear factor (NF)-κB activation; however, the underlying mechanism of CARMA3 in lung cancer stemness and metastasis remains largely unknown.Objectives: To investigate the molecular mechanisms underlying the involvement of CARMA3 in non–small cell lung cancer progression.Methods: The expression levels of CARMA3 and NME2 in a cohort of patients with lung cancer (n = 91) were examined by immunohistochemistry staining and assessed by Kaplan-Meier survival analysis. The effects of CARMA3, microRNA-182 (miR-182), and NME2 on cancer stemness and metastasis were measured in vitro and in vivo. Chromatin immunoprecipitation and luciferase reporter assays were performed to determine the mechanisms of NF-κB–driven miR-182 expression and NME2 regulation.Measurements and Main Results: We observed that CARMA3 inversely correlated with NME2 expression in patients with lung cancer (Pearson correlation coefficient:...