Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China.
Department of Clinical Laboratory Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, People's Republic of China.
J Cancer Res Ther. 2024 Aug 1;20(4):1323-1333. doi: 10.4103/jcrt.jcrt_558_24. Epub 2024 Aug 29.
Protein arginine deiminase 3 (PADI3) is involved in various biological processes of human disease. PADI3 has recently received increasing attention due to its role in tumorigenesis. In a previous study, we found that PADI3 plays a tumor suppressor role in colon cancer by inducing cell cycle arrest, but its critical role and mechanism in cancer metastasis remain obscure. In this study, we fully studied the role of PADI3 in colon cancer cell metastasis.
The expression levels of related proteins were detected by Western blotting, and Transwell and wound healing assays were used to examine the cell migration ability. Flow cytometry was used to measure and exclude cell apoptosis-affected cell migration. Both overexpression and rescue experiments were employed to elucidate the molecular mechanism of CKS1 in colon cancer cells.
The expression levels of PADI3 and CKS1 are negatively related, and PADI3 can promote CKS1 degradation in a ubiquitin-dependent manner. PADI3 can suppress colon cancer cell migration and reduce the wound healing speed by inhibiting CKS1 expression. The molecular mechanism showed that CKS1 can promote EMT by increasing Snail and N-cadherin expression and suppressing E-cadherin expression. PADI3, as a suppressor of CKS1, can block the process of EMT by impairing CKS1-induced Snail upregulation and E-cadherin downregulation; however, the expression of N-cadherin cannot be rescued.
CKS1 promotes EMT in colon cancer by regulating Snail/E-cadherin expression, and this effect can be reversed by PADI3 via the promotion of CKS1 degradation in a ubiquitylation-dependent manner.
精氨酸脱亚氨酶 3（PADI3）参与人类疾病的各种生物学过程。由于其在肿瘤发生中的作用，PADI3 最近受到越来越多的关注。在之前的研究中，我们发现 PADI3 通过诱导细胞周期停滞在结肠癌中发挥肿瘤抑制作用，但它在癌症转移中的关键作用和机制仍不清楚。在这项研究中，我们全面研究了 PADI3 在结肠癌细胞转移中的作用。
通过 Western blot 检测相关蛋白的表达水平，通过 Transwell 和划痕愈合实验检测细胞迁移能力。流式细胞术用于测量和排除受细胞凋亡影响的细胞迁移。过表达和挽救实验用于阐明 CKS1 在结肠癌细胞中的分子机制。
PADI3 和 CKS1 的表达水平呈负相关，PADI3 可以通过泛素依赖性方式促进 CKS1 降解。PADI3 可以通过抑制 CKS1 表达来抑制结肠癌细胞迁移并降低伤口愈合速度。分子机制表明，CKS1 通过增加 Snail 和 N-cadherin 的表达并抑制 E-cadherin 的表达来促进 EMT。作为 CKS1 的抑制剂，PADI3 可以通过破坏 CKS1 诱导的 Snail 上调和 E-cadherin 下调来阻断 EMT 过程；然而，N-cadherin 的表达不能被挽救。
CKS1 通过调节 Snail/E-cadherin 表达促进结肠癌细胞 EMT，PADI3 可以通过依赖泛素化的方式促进 CKS1 降解来逆转这种作用。
