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MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1

机译:MARCH9通过下调ICAM-1抑制肺腺癌的进展

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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.
机译:背景/目的探讨膜相关的RING-CH蛋白9(MARCH9)在肺腺癌(LAC)中的临床意义和功能机制。方法采用免疫组织化学方法检测MARCH9在LAC组织及邻近正常肺组织中的表达。使用总生存率评估患者的预后。 MARCH9的预后作用已通过单因素和多因素分析进行​​了测试。为了证实MARCH9在细胞增殖和侵袭中的作用,在两种LAC细胞系中诱导了MARCH9的过表达。进行了细胞周期,凋亡,迁移,侵袭和免疫沉淀实验,以进一步探索涉及的信号传导途径。结果对一系列143份临床样本的分析表明,与正常肺组织相比,MARCH9在肿瘤组织中被下调,并且与淋巴结转移密切相关(P = 0.004)。单因素和多因素分析表明,MARCH9是LAC的独立预后生物标志物。 MARCH9表达低表明总体存活率低。对A549和H1299细胞的细胞研究表明,MARCH9可以减弱肿瘤的迁移和侵袭,但对细胞周期或凋亡几乎没有影响。此外,鉴定了MARCH9和ICAM-1蛋白之间的相互作用,并且发现MARCH9的过表达减弱了ICAM-1的致癌作用,表明MARCH9可以通过下调ICAM-1信号转导来抑制肿瘤进展。结论LAC组织中MARCH9的下调与不良的临床预后相关。 MARCH9可用作LAC的新型生物标志物和潜在治疗靶标。

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