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组蛋白赖氨酸特异性去甲基化酶6B在胃癌中的表达模式

Expression pattern of histone lysine-specific demethylase 6B in gastric cancer.

作者信息

Wang Shujun, Wang Yiping, Zhu Hui, Chen Miaohui, Zhang Liang

机构信息

Department of Gastroenterology, Cixi People's Hospital, Affiliated Cixi Hospital, Wenzhou Medical University, Cixi, Zhejiang 315300, P.R. China.

出版信息

Oncol Lett. 2021 Jun;21(6):491. doi: 10.3892/ol.2021.12752. Epub 2021 Apr 26.

DOI:10.3892/ol.2021.12752
PMID:33968207
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8100944/
Abstract

Over the last few decades, predictive markers for the prognosis of gastric cancer have not been extensively investigated. The present study aimed to evaluate the expression profile of histone demethylase lysine (K)-specific demethylase 6B (KDM6B) in gastric cancer and healthy control tissues, as well as its value in prognosis prediction as a clinical marker. Within the framework of these criteria, the diagnostic role of KMD6B for gastric cancer was investigated, which may provide insights into novel treatment targets. Immunohistochemistry was applied to detect KMD6B expression in 100 gastric cancer tissues and matching para-cancerous tissues to analyze the association between KMD6B expression and clinicopathological features. Based on the follow-up data, the value of KMD6B in prognosis assessment was further explored. The role of KMD6B in gastric cancer cell proliferation, cell cycle distribution and the expression of cell cycle-associated proteins was investigated by inhibiting KMD6B activity using the specific inhibitor GSK J4. KMD6B was mostly distributed in cytoplasm and nucleus in gastric cancer tissue. The expression level was significantly higher in cancer tissues compared with that in the corresponding non-cancerous tissues. The expression of KMD6B was significantly associated with sex, lymph node and distant metastasis status and clinical stage (P<0.05). Cell proliferation was significantly decreased with the inhibition of KMD6B activity, and the cell cycle in HGC27 cells was arrested in the G/M phase after being treated with GSK J4 for 24 h. The expression of cyclin B and Cdc2 were significantly decreased, while p21 was upregulated. It was concluded that the dysregulated expression of KMD6B is associated with the malignant progression of gastric cancer and could be a potential marker for prognosis. Blocking the demethylase activity of KMD6B induced G/M arrest and inhibited the proliferation of gastric cancer cells, suggesting that KMD6B is a potential novel therapeutic target for gastric cancer.

摘要

在过去几十年中，尚未对胃癌预后的预测标志物进行广泛研究。本研究旨在评估组蛋白去甲基化酶赖氨酸（K）特异性去甲基化酶6B（KDM6B）在胃癌组织和健康对照组织中的表达谱，以及其作为临床标志物在预后预测中的价值。在这些标准的框架内，研究了KMD6B对胃癌的诊断作用，这可能为新的治疗靶点提供见解。应用免疫组织化学检测100例胃癌组织及配对癌旁组织中KMD6B的表达，分析KMD6B表达与临床病理特征的关系。基于随访数据，进一步探讨KMD6B在预后评估中的价值。使用特异性抑制剂GSK J4抑制KMD6B活性，研究KMD6B在胃癌细胞增殖、细胞周期分布及细胞周期相关蛋白表达中的作用。KMD6B在胃癌组织中主要分布于细胞质和细胞核。癌组织中的表达水平明显高于相应的非癌组织。KMD6B的表达与性别、淋巴结及远处转移状态和临床分期显著相关（P<0.05）。抑制KMD6B活性可显著降低细胞增殖，用GSK J4处理HGC27细胞24小时后，细胞周期停滞在G/M期。细胞周期蛋白B和Cdc2的表达明显降低，而p21上调。结论是，KMD6B的表达失调与胃癌的恶性进展相关，可能是一种潜在的预后标志物。阻断KMD6B的去甲基化酶活性可诱导G/M期阻滞并抑制胃癌细胞增殖，提示KMD6B是胃癌潜在的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/d0520f8e9988/ol-21-06-12752-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/3b959018f643/ol-21-06-12752-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/1e7d92ee6598/ol-21-06-12752-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/d0520f8e9988/ol-21-06-12752-g06.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/9b3bb393879d/ol-21-06-12752-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/3ed2a059d7eb/ol-21-06-12752-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/375a6bb5d812/ol-21-06-12752-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/486346884f5b/ol-21-06-12752-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/1e7d92ee6598/ol-21-06-12752-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b921/8100944/d0520f8e9988/ol-21-06-12752-g06.jpg

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