{"title":"Heparan sulfate 6-O-sulfotransferase 2 promotes gastric cancer progression by modulating the TGF-β/smad2/3 pathway.","authors":"Shuai Wu, Changqin Xu, Weijia Sun, Qianqian Xu, Feifei Zhou, Ruzhen Jia, Hongwei Xu","doi":"10.62347/LWZR1836","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in gastric cancer (GC).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>in vivo</i>.</p><p><strong>Conclusion: </strong>HS6ST2 promotes GC progression through the modulation of the TGF-β/smad2/3 pathway.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"16 12","pages":"7924-7936"},"PeriodicalIF":1.7000,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733364/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of translational research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/LWZR1836","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
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 in vivo.
Conclusion: HS6ST2 promotes GC progression through the modulation of the TGF-β/smad2/3 pathway.
目的：探讨硫酸肝素6- o -硫转移酶2 （HS6ST2）在胃癌（GC）中的作用。方法：采用免疫组化（IHC）法检测胃癌及邻近正常胃黏膜中HS6ST2的表达。观察HS6ST2表达水平与临床病理参数的相关性。Western blotting检测HS6ST2蛋白在AGS、MKN45和GES-1细胞中的表达。通过CCK-8、创面愈合和Transwell实验探讨HS6ST2在胃癌细胞中的功能。为了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：胃癌组织中HS6ST2的表达水平明显高于邻近正常胃黏膜，且与肿瘤大小呈正相关。与GES-1细胞相比，HS6ST2在AGS和MKN45细胞中的表达水平显著升高。沉默HS6ST2会损害GC细胞的生长、移动性和上皮-间质转化（EMT）。另一方面，HS6ST2的上调增加了GC细胞的生长、迁移和侵袭，而SB431542处理显著阻断了这一作用。此外，小鼠异种移植实验表明，HS6ST2沉默在体内抑制肿瘤生长和EMT。结论：HS6ST2通过调控TGF-β/smad2/3通路促进GC进展。
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