组蛋白去乙酰化酶2稳定SPARC相关模块化钙结合蛋白2以促进胆囊癌转移和干性
Histone Deacetylase 2 Stabilizes SPARC-related Modular Calcium Binding 2 to Promote Metastasis and Stemness in Gallbladder Cancer.
作者信息
Feng Ji, Zheng Xueyong
机构信息
Department of General Surgery, Sir Run Run Shaw Hospital (SRRSH), Affiliated with the Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310000, China.
出版信息
Curr Mol Med. 2025;25(1):56-68. doi: 10.2174/0115665240257970231013094101.
BACKGROUND
We aimed to investigate the relationship between histone deacetylase 2 (HDAC2) and SPARC-related modular calcium binding 2 (SMOC2) and the role of SMOC2 in gallbladder cancer (GBC).
METHODS
The expression of HDAC2 and SMOC2 in GBC and normal cells was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), which was also used to detect the mRNA stability of SMOC2. The combination between HDAC2 and SMOC2 was detected by Chromatin immunoprecipitation (ChIP) assay. After silencing and/or overexpressing HDAC2 and SMOC2, cell viability, migration, invasion, and stemness were respectively tested by the Cell Counting Kit-8 (CCK-8), cell scratch, transwell, and sphere-formation assay.
RESULTS
In GBC cells, HDAC2 and SMOC2 were highly expressed. HDAC2 combined with SMOC2 promoted mRNA stability of SMOC2. HDAC2 or SMOC2 overexpression promoted GBC cell metastasis and stemness. SMOC2 overexpression rescued the negative effects of silencing HDAC2 in GBC.
CONCLUSION
HDAC2 stabilizes SMOC2 to promote metastasis and stemness in gallbladder cancer.
背景
我们旨在研究组蛋白去乙酰化酶2（HDAC2）与富含半胱氨酸的酸性分泌蛋白相关的模块化钙结合蛋白2（SMOC2）之间的关系以及SMOC2在胆囊癌（GBC）中的作用。
方法
采用定量实时逆转录聚合酶链反应（qRT-PCR）检测HDAC2和SMOC2在GBC细胞和正常细胞中的表达，该方法还用于检测SMOC2的mRNA稳定性。通过染色质免疫沉淀（ChIP）分析检测HDAC2与SMOC2之间的结合。在沉默和/或过表达HDAC2和SMOC2后，分别通过细胞计数试剂盒-8（CCK-8）、细胞划痕、Transwell和球体形成试验检测细胞活力、迁移、侵袭和干性。
结果
在GBC细胞中，HDAC2和SMOC2高表达。HDAC2与SMOC2结合可促进SMOC2的mRNA稳定性。HDAC2或SMOC2过表达促进GBC细胞转移和干性。SMOC2过表达可挽救沉默HDAC2对GBC的负面影响。
结论
HDAC2使SMOC2稳定，从而促进胆囊癌的转移和干性。
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