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p97/ 泛素结合酶(VCP)及其互作蛋白小 SVIP 在胰腺癌侵袭迁移中的作用

The function of p97/valosin-containing protein (VCP) and small VCP-interacting protein (SVIP) in invasion and migration of pancreatic cancer cells.

机构信息

Department of Histology and Embryology, Faculty of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkiye.

出版信息

Turk J Med Sci. 2024 Jun 4;54(5):1154-1164. doi: 10.55730/1300-0144.5894. eCollection 2024.

Abstract

BACKGROUND/AIM: Misfolded proteins are eliminated by a process known as endoplasmic reticulum-associated protein degradation (ERAD). ERAD has an impact on a variety of illnesses, such as diabetes, cystic fibrosis, cancer, and neurological conditions. As one of the many proteins involved in ERAD, this study is focused on p97/valosin-containing protein (VCP) and small VCP-interacting protein (SVIP). The existence and function of SVIP and p97/VCP in various types of pancreatic cancer have not yet been investigated. The study's objectives are to examine the expressions of SVIP and p97/VCP in two pancreatic cancer types and to show whether these proteins aid in the invasion and migration of pancreatic cancer cells.

MATERIALS AND METHODS

In this work, MIA PaCa-2 and PANC-1 human cell lines were examined. Immunocytochemistry and immunofluorescence were performed to detect the cellular localization and presence of p97/VCP and SVIP in pancreatic cancer cells. Following p97/VCP siRNA and SVIP siRNA transfection of the cells, protein expressions were assessed using Western blot analysis. The effects of this suppression on cell invasion and migration were determined using the xCELLigence real-time analysis system (RTAC).

RESULTS

In the nucleus and cytoplasm of MIA PaCa-2 and PANC-1 cells, p97/VCP and SVIP immunoexpressions were seen. The decrease in protein expressions of p97/VCPsi and SVIPsi was significant in pancreatic cells compared to the controlsi. The p97/VCP siRNA transfection reduced the invasion and migration of MIA PaCa-2 and PANC-1 cells. In addition, the SVIP siRNA suppression resulted in increasing the invasion and migration ability of both cells. This study also demonstrated, for the first time, SVIP expression in MIA PaCa-2 and PANC-1 cells.

CONCLUSION

Overall, the findings show the differential expression and function of p97/VCP and SVIP in pancreas ductal adenocarcinoma cells. The potential of the pancreatic cancer cells to migrate and invade altered when the two cell lines were transfected with p97/VCPsi and SVIPsi.

摘要

背景/目的:错误折叠的蛋白质通过内质网相关蛋白降解(ERAD)过程被清除。ERAD 对多种疾病有影响,如糖尿病、囊性纤维化、癌症和神经疾病。作为 ERAD 涉及的众多蛋白质之一,本研究集中在 p97/ 包含 valosin 的蛋白(VCP)和小 VCP 相互作用蛋白(SVIP)上。SVIP 和 p97/VCP 在各种类型胰腺癌中的存在和功能尚未被研究过。本研究的目的是检测两种胰腺癌类型中 SVIP 和 p97/VCP 的表达情况,并表明这些蛋白质是否有助于胰腺癌细胞的侵袭和迁移。

材料和方法

在这项工作中,检查了 MIA PaCa-2 和 PANC-1 人细胞系。通过免疫细胞化学和免疫荧光检测胰腺癌细胞中 p97/VCP 和 SVIP 的细胞定位和存在。在对细胞进行 p97/VCP siRNA 和 SVIP siRNA 转染后,使用 Western blot 分析评估蛋白质表达。使用 xCELLigence 实时分析系统(RTAC)确定这种抑制对细胞侵袭和迁移的影响。

结果

在 MIA PaCa-2 和 PANC-1 细胞的核和细胞质中,观察到 p97/VCP 和 SVIP 的免疫表达。与对照 si 相比,胰腺细胞中 p97/VCPsi 和 SVIPsi 的蛋白质表达下降显著。p97/VCP siRNA 转染降低了 MIA PaCa-2 和 PANC-1 细胞的侵袭和迁移。此外,SVIP siRNA 抑制导致两种细胞的侵袭和迁移能力增加。本研究还首次证明了 SVIP 在 MIA PaCa-2 和 PANC-1 细胞中的表达。

结论

总的来说,研究结果表明 p97/VCP 和 SVIP 在胰腺导管腺癌细胞中的表达和功能存在差异。当用 p97/VCPsi 和 SVIPsi 转染两条细胞系时,胰腺癌细胞的迁移和侵袭能力发生了改变。

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