MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1

Abstract

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.

The Membrane-Associated MARCH E3 Ligase Family: Emerging Roles in Immune Regulation

“…It has been demonstrated that overexpression of MARCH9 mediates polyubiquitination of ICAM-1 for lysosome-dependent degradation (20). MARCH9 attenuates the oncogenic effects of ICAM-1, leading to the inhibition of migration and invasion in lung adenocarcinoma (LAC) cells (93). Interestingly, MARCH9 down-regulation in LAC correlates with poor clinical outcomes (93).…”

“…MARCH9 attenuates the oncogenic effects of ICAM-1, leading to the inhibition of migration and invasion in lung adenocarcinoma (LAC) cells (93). Interestingly, MARCH9 down-regulation in LAC correlates with poor clinical outcomes (93).…”

<p>LncRNA HOTAIRM1 Inhibits the Proliferation and Invasion of Lung Adenocarcinoma Cells via the miR-498/WWOX Axis</p>

“…Lung cancer, one of the most commonly diagnosed malignant tumors, is a major cause of cancer-related deaths around the world. 1,2 Lung cancer can be categorized into five histological types: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell carcinoma, and bronchoalveolar carcinoma. 3,4 Among them, lung adenocarcinoma (ADC) is the most prevalent and has high metastatic and invasion likelihood.…”

Lidocaine inhibited migration of NSCLCA549 cells via the CXCR4 regulation

“…CD44 has been wildly used as a key migration-related biomarker for lung cancers [ 54 , 55 ]. Another migration-related extracellular molecule, ICAM-1, is also thought to be critical in lung cancer cell migration [ 56 , 57 , 58 ]. Both CD44 and ICAM-1 levels were significantly increased by CXCL12.…”