高级检索
当前位置: 首页 > 详情页

Downregulation of NMI promotes tumor growth and predicts poor prognosis in human lung adenocarcinomas

文献详情

资源类型:
机构: [1]Sun Yat-sen University Cancer Center [2] State Key Laboratory of Oncology in South China [3] Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. [2]Shunde Hospital, Southern Medical University, Foshan, China. [3]The First Affiliated Hospital of Dalian Medical University, Dalian, China. [4]Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. [5]Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China. [6]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [7]State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
出处:
ISSN:

关键词: NMI COX-2 NF-kappa B p300 Lung cancer

摘要:
Background: N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth, progression, and metastasis. In this study, we identified NMI as a potential tumor suppressor in lung cancer and explored its molecular mechanism involved in lung cancer progression. Methods: Human lung cancer cell lines and a mouse xenograft model was used to study the effect of NMI on tumor growth. The expression of NMI, COX-2 and relevant signaling proteins were examined by Western blot. Tissue microarray immunohistochemical analysis was performed to assess the correlation between NMI and COX-2 expression in lung cancer patients. Results: NMI was highly expressed in normal lung cells and tissues, but lowly expressed in lung cancer cells and tissues. Overexpression of NMI induced apoptosis, suppressed lung cancer cell growth and migration, which were mediated by up-regulation of the cleaved caspase-3/9 and down-regulation of phosphorylated PI3K/AKT, MMP2/MMP9, beta-cadherin, and COX-2/PGE2. In contrast, knockdown of NMI promoted lung cancer cell colony formation and migration, which were correlated with the increased expression of phosphorylated PI3K/AKT, MMP2/MMP9, beta-cadherin and COX-2/PGE2. Further study showed that NMI suppressed COX-2 expression through inhibition of the p50/p65 NF-kappa B acetylation mediated by p300. The xenograft lung cancer mouse models also confirmed the NMI-mediated suppression of tumor growth by inhibiting COX-2 signaling. Moreover, tissue microarray immunohistochemical analysis of lung adenocarcinomas also demonstrated a negative correlation between NMI and COX-2 expression. Kaplan-Meier analysis indicated that the patients with high level of NMI had a significantly better prognosis. Conclusions: Our study showed that NMI suppressed tumor growth by inhibiting PI3K/AKT, MMP2/MMP9, COX-2/PGE2 signaling pathways and p300-mediated NF-kappa B acetylation, and predicted a favorable prognosis in human lung adenocarcinomas, suggesting that NMI was a potential tumor suppressor in lung cancer.

基金:
语种:
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 生化与分子生物学 2 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 肿瘤学
第一作者:
第一作者机构: [1]Sun Yat-sen University Cancer Center [5]Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
共同第一作者:
通讯作者:
通讯机构: [1]Sun Yat-sen University Cancer Center [2] State Key Laboratory of Oncology in South China [2]Shunde Hospital, Southern Medical University, Foshan, China. [7]State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:43389 今日访问量:0 总访问量:3120 更新日期:2024-09-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 四川省肿瘤医院 技术支持:重庆聚合科技有限公司 地址:成都市人民南路四段55号