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食管鳞状细胞癌细胞系中S-腺苷同型半胱氨酸水解酶(SAHH)的过表达:对细胞凋亡、迁移和黏附的影响

Overexpression of S-adenosylhomocysteine hydrolase (SAHH) in esophageal squamous cell carcinoma (ESCC) cell lines: effects on apoptosis, migration and adhesion of cells.

作者信息

Li Qinghua, Mao Lihong, Wang Ruili, Zhu Liqiang, Xue Lexun

机构信息

Laboratory for Cell Biology, The First Affiliated Hospital, Zhengzhou University, 40 Daxue Road, Henan, 450052, China.

出版信息

Mol Biol Rep. 2014;41(4):2409-17. doi: 10.1007/s11033-014-3095-8. Epub 2014 Jan 16.

Abstract

S-adenosylhomocysteine hydrolase (SAHH) is the sole enzyme that catalyses the hydrolysis of S-adenosylhomocysteine (SAH) in methylation reaction. Previous studies have shown that its inhibition or deficiency leads to several human disorders such as severe coagulopathy, hepatopathy and myopathy. However, the effects of SAHH on esophageal squamous cell carcinoma (ESCC) cells have not been explored so far. To determine whether SAHH is involved in carcinogenesis of the esophagus, we investigated the expression of SAHH in ESCC and normal esophageal epithelial cells and found that SAHH was downregulated in ESCC cells compared with normal esophageal epithelial cells (P < 0.05). The overexpressed SAHH in ESCC cells promoted cell apoptosis, inhibited cell migration and adhesion, but did not affect the cell proliferation and cell cycle. Furthermore, an interaction of SAHH with receptor of activated C kinase 1 (RACK1) protein was detected by coimmunoprecipitation and an increased RACK1, which is caused by overexpression of SAHH, was verified by Western blotting. The findings mentioned above demonstrate that SAHH can promote apoptosis, inhibit migration and adhesion of ESCC cells suggesting that it may be involved in carcinogenesis of the esophagus.

摘要

S-腺苷同型半胱氨酸水解酶(SAHH)是甲基化反应中唯一催化S-腺苷同型半胱氨酸(SAH)水解的酶。先前的研究表明,其抑制或缺乏会导致多种人类疾病,如严重的凝血病、肝病和肌病。然而,迄今为止,尚未探索SAHH对食管鳞状细胞癌(ESCC)细胞的影响。为了确定SAHH是否参与食管癌的发生,我们研究了SAHH在ESCC细胞和正常食管上皮细胞中的表达,发现与正常食管上皮细胞相比,ESCC细胞中SAHH表达下调(P<0.05)。ESCC细胞中过表达的SAHH促进细胞凋亡,抑制细胞迁移和黏附,但不影响细胞增殖和细胞周期。此外,通过免疫共沉淀检测到SAHH与活化C激酶1(RACK1)蛋白受体之间存在相互作用,并且通过蛋白质印迹法证实了由SAHH过表达引起的RACK1增加。上述研究结果表明,SAHH可促进ESCC细胞凋亡,抑制其迁移和黏附,提示其可能参与食管癌的发生。

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