硫酸乙酰肝素6-O-磺基转移酶2通过调节TGF-β/smad2/3信号通路促进胃癌进展。
Heparan sulfate 6-O-sulfotransferase 2 promotes gastric cancer progression by modulating the TGF-β/smad2/3 pathway.
作者信息
Wu Shuai, Xu Changqin, Sun Weijia, Xu Qianqian, Zhou Feifei, Jia Ruzhen, Xu Hongwei
机构信息
Department of Gastroenterology, Shandong Provincial Hospital, Shandong University Jinan 250014, Shandong, China.
Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Jinan 250014, Shandong, China.
出版信息
Am J Transl Res. 2024 Dec 15;16(12):7924-7936. doi: 10.62347/LWZR1836. eCollection 2024.
OBJECTIVE
To investigate the role of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in gastric cancer (GC).
METHODS
HS6ST2 expression in GC and adjacent normal gastric mucosa was first detected via immunohistochemical (IHC) staining. The correlation between the expression level of HS6ST2 and clinicopathological parameters were observed. The protein expression of HS6ST2 in AGS, MKN45 and GES-1 cells was examined using Western blotting. The function of HS6ST2 in GC cells was explored via CCK-8, wound healing and Transwell assays. To elucidate the underlying molecular mechanisms, we detected whether HS6ST2 modulated the TGF-β/smad2/3 signaling pathway. Finally, we investigated the role of HS6ST2 in tumor growth in a nude mouse model.
RESULTS
The expression level of HS6ST2 in GC tissues was significantly higher than that in adjacent normal gastric mucosa and was positively correlated with tumor size. Compared with GES-1 cells, the expression level of HS6ST2 in AGS and MKN45 cells was significantly elevated. Silencing HS6ST2 impaired GC cell growth, mobility and epithelial-mesenchymal transition (EMT). On the other hand, HS6ST2 upregulation increased GC cell growth, migration and invasion, which was dramatically blocked by SB431542 treatment. Furthermore, mouse xenograft experiments demonstrated that HS6ST2 silencing inhibited tumor growth and EMT .
CONCLUSION
HS6ST2 promotes GC progression through the modulation of the TGF-β/smad2/3 pathway.
目的
探讨硫酸乙酰肝素6 - O -磺基转移酶2（HS6ST2）在胃癌（GC）中的作用。
方法
首先通过免疫组织化学（IHC）染色检测HS6ST2在胃癌及癌旁正常胃黏膜中的表达。观察HS6ST2表达水平与临床病理参数之间的相关性。采用蛋白质免疫印迹法检测AGS、MKN45和GES - 1细胞中HS6ST2的蛋白表达。通过CCK - 8、伤口愈合和Transwell实验探讨HS6ST2在胃癌细胞中的功能。为阐明潜在的分子机制，我们检测了HS6ST2是否调节TGF -β/smad2/3信号通路。最后，我们在裸鼠模型中研究了HS6ST2在肿瘤生长中的作用。
结果
HS6ST2在胃癌组织中的表达水平显著高于癌旁正常胃黏膜，且与肿瘤大小呈正相关。与GES - 1细胞相比，AGS和MKN45细胞中HS6ST2的表达水平显著升高。沉默HS6ST2会损害胃癌细胞的生长、迁移能力和上皮 - 间质转化（EMT）。另一方面，HS6ST2的上调增加了胃癌细胞的生长、迁移和侵袭，而SB431542处理可显著阻断这种作用。此外，小鼠异种移植实验表明，沉默HS6ST2可抑制肿瘤生长和EMT。
结论
HS6ST2通过调节TGF -β/smad2/3通路促进胃癌进展。
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