MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1

Cellular Physiology and Biochemistry

Qi-ming Shen¹ 

关键词: Lung adenocarcinoma;    MARCH9;    Invasion;    Prognosis;   

DOI  :  10.1159/000493961

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims To investigate the clinical significance and functional mechanisms of membrane-associated RING-CH protein 9 (MARCH9) in lung adenocarcinoma (LAC). Methods Immunohistochemistry staining was performed to explore the expression of MARCH9 in LAC tissues and adjacent normal lung tissues. Patients’ prognosis was evaluated using overall survival. The prognostic role of MARCH9 was tested with univariate and multivariate analyses. To confirm the effect of MARCH9 in cell proliferation and invasion, overexpression of MARCH9 was induced in two LAC cell lines. Cell cycle, apoptosis, migration, invasion, and immunoprecipitation experiments were performed to further explore the signaling pathways involved. Results Analysis of a series of 143 clinical samples revealed that MARCH9 was down-regulated in tumor tissues compared with normal lung tissues, and this was closely associated with lymph node metastasis (P = 0.004). Univariate and multivariate analyses indicated that MARCH9 was an independent prognostic biomarker for LAC; low MARCH9 expression indicated poor overall survival. Cellular studies with A549 and H1299 cells demonstrated that MARCH9 can attenuate tumor migration and invasion but had little effect on cell cycle or apoptosis. Moreover, an interaction between MARCH9 and ICAM-1 protein was identified, and overexpression of MARCH9 was found to attenuate the oncogenic effect of ICAM-1, suggesting that MARCH9 may inhibit tumor progression by downregulating ICAM-1 signaling. Conclusion MARCH9 downregulation in LAC tissues correlated with poor clinical outcomes. MARCH9 may serve as a novel biomarker and potential therapeutic target for LAC.

【 授权许可】

CC BY-NC-ND