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AEBP1 通过激活 NF-κB 通路促进胃癌细胞上皮-间充质转化,并预测患者的不良预后。

AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-κB pathway and predicts poor outcome of the patients.

机构信息

Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.

Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, China.

出版信息

Sci Rep. 2018 Aug 10;8(1):11955. doi: 10.1038/s41598-018-29878-6.

DOI:10.1038/s41598-018-29878-6
PMID:30097586
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6086860/
Abstract

Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. Recent studies have indicated that AEBP1 might function as a candidate oncogene and is overexpressed in several human malignancies. However, the role of AEBP1 in gastric cancer (GC) remains largely unknown. This study aimed to investigate the expression pattern, prognostic significance and biological function of AEBP1 in human gastric cancer and to explore the underlying mechanism. We found that both the mRNA and protein levels of AEBP1 were significantly increased in human GC tissues. Elevated AEBP1 expression was significantly correlated with poor overall survival in patients with both early-stage (Tumor, Node, Metastases (TNM) TNM I and II) and late-stage (TNM III and IV) GC. Silencing AEBP1 markedly suppressed the proliferation, migration, invasion, metastasis and epithelial-mesenchymal transition of GC cells. Moreover, we demonstrated that knockdown of AEBP1 in GC cells led to inhibition of the NF-κB pathway by hampering the degradation of IκBα. Thus, AEBP1 might be served as a promising prognostic indicator and a potential therapeutic target in human GC.

摘要

脂肪细胞增强结合蛋白 1(AEBP1)是一种转录抑制因子,在调节脂肪生成中起着关键作用。最近的研究表明,AEBP1 可能作为候选癌基因发挥作用,并在几种人类恶性肿瘤中过度表达。然而,AEBP1 在胃癌(GC)中的作用在很大程度上尚不清楚。本研究旨在探讨 AEBP1 在人类胃癌中的表达模式、预后意义和生物学功能,并探讨其潜在机制。我们发现,AEBP1 的 mRNA 和蛋白水平在人 GC 组织中均显著升高。AEBP1 表达升高与早期(肿瘤、淋巴结、转移(TNM)TNM I 和 II)和晚期(TNM III 和 IV)GC 患者的总生存期不良显著相关。沉默 AEBP1 可显著抑制 GC 细胞的增殖、迁移、侵袭、转移和上皮-间充质转化。此外,我们证明 GC 细胞中 AEBP1 的敲低通过阻止 IκBα 的降解来抑制 NF-κB 途径。因此,AEBP1 可能成为人类 GC 有前途的预后指标和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/104a2f78c790/41598_2018_29878_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/104a2f78c790/41598_2018_29878_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/8892220ebe97/41598_2018_29878_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/e2c1edb94b34/41598_2018_29878_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/c331d285eaee/41598_2018_29878_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/a266bcba68a1/41598_2018_29878_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77a/6086860/5c16a4be02da/41598_2018_29878_Fig6_HTML.jpg
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