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AEBP1,一个预后指标,通过 NF-κB 通路促进结肠腺癌细胞的生长和转移。

AEBP1, a prognostic indicator, promotes colon adenocarcinoma cell growth and metastasis through the NF-κB pathway.

机构信息

Department of Colorectal Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.

Department of General Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.

出版信息

Mol Carcinog. 2019 Oct;58(10):1795-1808. doi: 10.1002/mc.23066. Epub 2019 Jun 10.

Abstract

The abnormal expression of adipocyte enhancer binding protein 1 (AEBP1) has been implicated in the carcinogenesis and progression of various types of human tumors. However, the role of AEBP1 in colon adenocarcinoma (COAD) remains largely unelucidated. In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. In addition, univariate and multivariate Cox regression analyses revealed that high AEBP1 expression suggested poor prognosis in COAD. Moreover, AEBP1 silencing suppressed COAD cell proliferation, migration, and invasion, whereas the upregulation of AEBP1 promoted these behaviors. Additionally, mechanistic studies further demonstrated that AEBP1 promoted COAD cell proliferation, migration, and invasion by upregulating the expression of matrix metalloproteinase-2, vimentin, and TWIST whereas downregulating that of E-cadherin through the nuclear factor-κB pathway. Collectively, these data indicated that AEBP1 may be a new prognostic factor and a potential gene therapy target in COAD.

摘要

脂肪细胞增强结合蛋白 1(AEBP1)的异常表达与多种人类肿瘤的发生和进展有关。然而,AEBP1 在结肠腺癌(COAD)中的作用在很大程度上仍未阐明。在这项研究中,我们探讨了 AEBP1 在 COAD 中的临床意义和生物学功能。我们观察到 AEBP1 在 COAD 组织和细胞中过表达,AEBP1 的表达与 COAD 患者的肿瘤大小、组织学分化程度、淋巴结转移和癌症分期相关。此外,单因素和多因素 Cox 回归分析显示,AEBP1 高表达提示 COAD 预后不良。此外,AEBP1 沉默抑制 COAD 细胞增殖、迁移和侵袭,而 AEBP1 的上调则促进这些行为。此外,机制研究进一步表明,AEBP1 通过核因子-κB 通路上调基质金属蛋白酶-2、波形蛋白和 TWIST 的表达,下调 E-钙黏蛋白的表达,从而促进 COAD 细胞的增殖、迁移和侵袭。综上所述,这些数据表明 AEBP1 可能是 COAD 的一个新的预后因素和潜在的基因治疗靶点。

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