26 引文 斯高帕斯(Scopus)

摘要

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: R = -0.24; P = 0.022). NME2 levels were significantly decreased in tumor tissues compared with adjacent normal lung tissues (P <0.001), and patients with lung cancer with higher levels of NME2 had longer survival outcomes (overall survival, P <0.01; disease-free survival, P <0.01). Mechanistically, CARMA3 promoted cell motility by reducing the level of NME2 through the NF-κB/miR-182 pathway and by increasing cancer stem cell properties and metastasis in lung cancer. Conclusions: We identified a novel mechanism of CARMA3 in lung cancer stemness and metastasis through the negative regulation of NME2 by NF-κB-dependent induction of miR-182. Our findings provide an attractive strategy for targeting the CARMA3/NF-κB/miR-182 pathway as a potential treatment for lung cancer.
原文英語
頁(從 - 到)64-75
頁數12
期刊American Journal of Respiratory and Critical Care Medicine
192
發行號1
DOIs
出版狀態已發佈 - 7月 1 2015

ASJC Scopus subject areas

  • 肺和呼吸系統醫學
  • 重症監護和重症監護醫學

指紋

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