Overexpression of heat shock protein 47 is associated with increased proliferation and metastasis in gastric cancer.

Jieun Lee, Jung-Ah Hwang, Seung-Hyun Hong, Seon-Young Kim, Donghyeok Seol, Il Ju Choi, Yeon-Su Lee
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Abstract

Here, we investigated that the heat shock protein 47 (HSP47) plays a crucial role in the progression of gastric cancer (GC). We analyzed HSP47 gene expression in GC cell lines and patient tissues. The HSP47 mRNA and protein expression levels were significantly higher in GC cell lines and tumor tissues compared to normal gastric mucosa. Using siRNA to silence the expression of HSP47 in GC cells resulted in a significant reduction in their proliferation, wound healing, migration, and invasion capacities. Additionally, we also showed that the mRNA expression of matrix metallopeptidase-7 (MMP-7), a metastasis-promoting gene, was significantly reduced in HSP47 siRNA-transfected GC cells. We confirmed that the HSP47 promoter region was methylated in the SNU-216 GC cell line expressing low levels of HSP47 and in most non-cancerous gastric tissues. It means that the expression of HSP47 is regulated by epigenetic regulatory mechanisms. These findings suggest that targeting HSP47, potentially through its promoter methylation, could be a useful new therapeutic strategy for treating GC.

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热休克蛋白 47 的过表达与胃癌的增殖和转移有关。
在此,我们研究了热休克蛋白 47(HSP47)在胃癌(GC)进展过程中的关键作用。我们分析了 HSP47 在胃癌细胞系和患者组织中的基因表达。与正常胃黏膜相比,HSP47 mRNA和蛋白在胃癌细胞系和肿瘤组织中的表达水平明显更高。使用 siRNA 沉默 HSP47 在 GC 细胞中的表达会显著降低其增殖、伤口愈合、迁移和侵袭能力。此外,我们还发现在转染了 HSP47 siRNA 的 GC 细胞中,促进转移的基质金属肽酶-7(MMP-7)的 mRNA 表达明显减少。我们证实,在表达低水平 HSP47 的 SNU-216 GC 细胞系和大多数非癌胃组织中,HSP47 启动子区域被甲基化。这意味着HSP47的表达受到表观遗传调控机制的调控。这些研究结果表明,通过启动子甲基化来靶向 HSP47 可能是治疗 GC 的一种有用的新治疗策略。
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