KDM1A Acts as an Oncogene and Facilitates the Epithelial Mesenchymal Transition Process in Gastric Cancer

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biochemical and Molecular Toxicology Pub Date : 2025-02-05 DOI:10.1002/jbt.70120
Rongjie Huang, Yichen Cai, Qiuxian Chen, Yuqin Sun, Mingqiao Lian, Mingjie Lian, Lisheng Cai
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Abstract

Background

This study is performed to research the biological role of KDM1A in the epithelial mesenchymal transition (EMT) of gastric cancer and investigate the mechanism involved.

Methods

The KDM1A, Vimentin and E-cadherin levels were studied, as well as the correlation among them in gastric cancer samples. Gastric cancer cells were transfected with KDM1A overexpression and knockdown, and the cellular infiltration, motility, morphology and F-actin expression were subsequently identified. For the protein level assessment of EMT, the western blot analysis combined with immunofluorescence was employed. The effect of KDM1A on TGF-β/Notch signaling was also detected.

Results

KDM1A was overexpressed in gastric cancer tumor tissues. In the clinical gastric carcinoma samples, the level of KDM1A was linked negatively to the expression of E-cadherin, while positively to the expression of Vimentin. Among the gastric carcinoma population, the expression of KDM1A was linked to the lymph node metastasis, TNM stage and tumor differentiation. The KDM1A downregulation prohibited the cellular motility, infiltration and F-actin expression, and suppressed EMT process. KDM1A overexpression exhibited promoting effect on EMT in gastric cancer cells. KDM1A regulated TGF-β/Notch signaling to affect EMT in gastric cancer cells.

Conclusion

KDM1A acts as an oncogene and facilitates the epithelial mesenchymal transition process by regulating TGF-β/Notch signal pathway in gastric cancer cells.

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KDM1A作为癌基因促进胃癌上皮间质转化过程
背景:本研究旨在研究KDM1A在胃癌上皮间充质转化(epithelial mesenchymal transition, EMT)中的生物学作用,并探讨其机制。方法:研究胃癌标本中KDM1A、Vimentin、E-cadherin水平及其相关性。转染KDM1A过表达和低表达的胃癌细胞,随后检测细胞浸润、运动、形态和F-actin表达。采用western blot联合免疫荧光法评估EMT蛋白水平。KDM1A对TGF-β/Notch信号通路的影响也被检测。结果:KDM1A在胃癌肿瘤组织中过表达。在临床胃癌样本中,KDM1A水平与E-cadherin表达呈负相关,与Vimentin表达呈正相关。在胃癌人群中,KDM1A的表达与淋巴结转移、TNM分期和肿瘤分化有关。KDM1A的下调抑制了细胞的运动、浸润和F-actin的表达,抑制了EMT过程。KDM1A过表达对胃癌细胞EMT有促进作用。KDM1A调节TGF-β/Notch信号影响胃癌细胞EMT。结论:KDM1A在胃癌细胞中发挥致癌基因作用,通过调控TGF-β/Notch信号通路促进上皮间质转化过程。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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