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BBOX1-AS1通过与CtBP2相互作用促进贲门腺癌进展，以促进上皮-间质转化过程。

BBOX1-AS1 promotes gastric cardia adenocarcinoma progression via interaction with CtBP2 to facilitate the epithelial-mesenchymal transition process.

作者信息

Zou Wenxu, Yin Qing, Guo Wei, Dong Zhiming, Guo Yanli

机构信息

Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Cancer Sci. 2024 Dec;115(12):3875-3889. doi: 10.1111/cas.16350. Epub 2024 Sep 24.

DOI:10.1111/cas.16350
PMID:39318101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11611761/
Abstract

It is recognized that lncRNA BBOX1-AS1 exerts a crucial oncogenic property in several cancer types. However, the functions and underlying mechanisms of BBOX1-AS1 in the epithelial-mesenchymal transition (EMT) process of gastric cardia adenocarcinoma (GCA) have remained unclarified. The findings of this study demonstrated that GCA tissues had elevated BBOX1-AS1 expression levels, which was associated with a worse prognosis in GCA patients. BBOX1-AS1 dramatically enhanced cell proliferation, invasion, and TGF-β1-induced the EMT process in vitro. Further mechanism analysis revealed that BBOX1-AS1 could combine with CtBP2 and strengthen the interaction of CtBP2 and ZEB1. BBOX1-AS1 might regulate the E-cadherin expression through CtBP2/ZEB1 transcriptional complex-mediated transcriptional repression, further affecting the activation of the Wnt/β-catenin pathway and the EMT process. Overall, our findings demonstrate that BBOX1-AS1 might act as an lncRNA associated with EMT for facilitating GCA advancement via interaction with CtBP2 to facilitate the activation of Wnt/β-catenin pathway and the EMT process, which indicated that it might function as an exploitable treatment target for GCA patients.

摘要

人们认识到，长链非编码RNA BBOX1-AS1在几种癌症类型中发挥着关键的致癌作用。然而，BBOX1-AS1在贲门腺癌（GCA）上皮-间质转化（EMT）过程中的功能及潜在机制仍不清楚。本研究结果表明，GCA组织中BBOX1-AS1表达水平升高，这与GCA患者较差的预后相关。BBOX1-AS1在体外显著增强细胞增殖、侵袭及TGF-β1诱导的EMT过程。进一步的机制分析显示，BBOX1-AS1可与CtBP2结合并增强CtBP2与ZEB1的相互作用。BBOX1-AS1可能通过CtBP2/ZEB1转录复合物介导的转录抑制来调节E-钙黏蛋白的表达，进而影响Wnt/β-连环蛋白通路的激活及EMT过程。总体而言，我们的研究结果表明，BBOX1-AS1可能作为一种与EMT相关的长链非编码RNA，通过与CtBP2相互作用促进Wnt/β-连环蛋白通路的激活及EMT过程，从而推动GCA进展，这表明它可能成为GCA患者的一个可利用的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/732013e5249e/CAS-115-3875-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/24c2a38423e0/CAS-115-3875-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/5c70adf2587c/CAS-115-3875-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/3716b3caf3a8/CAS-115-3875-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/cd378d350ffd/CAS-115-3875-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/9faef11aa64b/CAS-115-3875-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/c6ddc51f0a18/CAS-115-3875-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/732013e5249e/CAS-115-3875-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/24c2a38423e0/CAS-115-3875-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/5c70adf2587c/CAS-115-3875-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/3716b3caf3a8/CAS-115-3875-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/cd378d350ffd/CAS-115-3875-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/9faef11aa64b/CAS-115-3875-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/c6ddc51f0a18/CAS-115-3875-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b912/11611761/732013e5249e/CAS-115-3875-g002.jpg

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[1]
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[3]
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[5]
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[9]
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[10]
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引用本文的文献

[1]
Analysis of the loss of Epithelial Cadherin expression in gastric cancer in Zambia.

Med J Zambia. 2025

本文引用的文献

[1]
RNA regulatory mechanisms controlling TGF-β signaling and EMT in cancer.

Semin Cancer Biol. 2024-7

[2]
Cross-Talk between the TGF-β and Cell Adhesion Signaling Pathways in Cancer.

Int J Med Sci. 2024

[3]
Cells of the tumor microenvironment speak the Wnt language.

Trends Mol Med. 2023-6

[4]
BBOX1-AS1 Activates Hedgehog Signaling Pathway to Facilitate the Proliferation and Stemness of Esophageal Squamous Cell Carcinoma Cells miR-506-5p/EIF5A/PTCH1 Axis.

Curr Mol Pharmacol. 2023

[5]
Population-based investigation of common and deviating patterns of gastric cancer and oesophageal cancer incidence across populations and time.

Gut. 2023-5

[6]
lncRNA BBOX1-AS1 silencing inhibits esophageal squamous cell cancer progression by promoting ferroptosis via miR-513a-3p/SLC7A11 axis.

Eur J Pharmacol. 2022-11-5

[7]
Long non-coding RNA BBOX1-antisense RNA 1 enhances cell proliferation and migration and suppresses apoptosis in oral squamous cell carcinoma via the miR-3940-3p/laminin subunit gamma 2 axis.

Bioengineered. 2022-4

[8]
Trends in the Incidence of Upper Gastrointestinal Cancers Show Changing Dynamics.

Clin Gastroenterol Hepatol. 2023-5

[9]
Long non-coding RNA BBOX1-AS1 exacerbates esophageal squamous cell carcinoma development by regulating HOXB7/β-catenin axis.

Exp Cell Res. 2022-6-1

[10]
LncRNA BBOX1-AS1 promotes pituitary adenoma progression via sponging miR-361-3p/E2F1 axis.

Anticancer Drugs. 2022-8-1

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