Department of Gastrointestinal and Pancreatic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland).
Med Sci Monit. 2018 Apr 24;24:2508-2517. doi: 10.12659/msm.906852.
BACKGROUND Myosin phosphatase target subunit 1 (MYPT1) serves as a subgroup of myosin phosphatases, and is frequently low-expressed in human cancers. However, little is known about the effects of MYPT1 in gastric cancer (GC). MATERIAL AND METHODS In our study, MYPT1 expression was detected by quantitative real-time reverse transcription PCR (qRT-PCR) in GC tissues, different advanced pathological stages of GC tissues, and preoperative and postoperative patients. Kaplan-Meier analysis was used to measure the overall survival of GC patients. MYPT1 expression was analyzed by qRT-PCR and Western blot assays in GES-1 cells and GC cells. Cell proliferation, cycle, and migration and invasion abilities were detected by CCK-8, flow cytometry, and Transwell assays. E-cadherin, TIMP-2, MMP-2, MMP-9 RhoA, and p-RhoA expressions were assessed by qRT-PCR and Western blot assays in treated SNU-5 cells. RESULTS Our results indicated that MYPT1 was down-regulated in GC tissues and cells, and is related to clinical stages and overall survival of GC. Functional research demonstrated that overexpression of MYPT1 can inhibit cell proliferation, cell cycle progression, and migration and invasion of GC cells. Many studies on mechanisms reported that overexpression of MYPT1 dramatically improved the expression levels of cell cycle-related genes (Cyclin D1 and c-myc), significantly increased epithelial marker (E-cadherin) expression, and decreased invasion-associated genes (TIMP-2 and MMP-2) expressions in SNU-5 cells. In addition, we found that MYPT1 suppressed RhoA phosphorylation. CONCLUSIONS We verified that MYPT1 inhibits GC cell proliferation and metastasis by regulating RhoA phosphorylation.
肌球蛋白磷酸酶靶蛋白 1（MYPT1）作为肌球蛋白磷酸酶的亚基，在人类癌症中表达水平通常较低。然而，关于 MYPT1 在胃癌（GC）中的作用知之甚少。
在我们的研究中，通过定量实时逆转录 PCR（qRT-PCR）检测 GC 组织、不同晚期 GC 组织以及术前和术后患者中的 MYPT1 表达。Kaplan-Meier 分析用于测量 GC 患者的总生存率。通过 qRT-PCR 和 Western blot 分析在 GES-1 细胞和 GC 细胞中检测 MYPT1 表达。通过 CCK-8、流式细胞术和 Transwell 测定检测细胞增殖、周期和迁移及侵袭能力。通过 qRT-PCR 和 Western blot 分析评估处理后的 SNU-5 细胞中 E-钙黏蛋白、TIMP-2、MMP-2、MMP-9、RhoA 和 p-RhoA 的表达。
我们的结果表明，MYPT1 在 GC 组织和细胞中下调，与 GC 的临床分期和总生存率相关。功能研究表明，过表达 MYPT1 可抑制 GC 细胞的增殖、细胞周期进程以及迁移和侵袭。许多关于机制的研究报告称，过表达 MYPT1 可显著提高细胞周期相关基因（Cyclin D1 和 c-myc）的表达水平，显著增加上皮标记物（E-钙黏蛋白）的表达，并降低 SNU-5 细胞中侵袭相关基因（TIMP-2 和 MMP-2）的表达。此外，我们发现 MYPT1 抑制 RhoA 磷酸化。
我们验证了 MYPT1 通过调节 RhoA 磷酸化抑制 GC 细胞的增殖和转移。
