Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
Xiao-Yu Chen and Sheng-Yong Yang contributed equally to this article.
Cell Transplant. 2021 Jan-Dec;30:9636897211053203. doi: 10.1177/09636897211053203.
Methionine sulfoxide reductase B1 (MsrB1) can catalyze both free and protein-bound R-methionine sulfoxides (R-MetO) to methionine (Met). It has been reported that MsrB1 plays an important role in the development of HCC and human bone osteosarcoma. However, little is known about the functions of MsrB1 in human colorectal cancer (CRC). Herein, we detected MsrB1 expression level in CRC tissue and cell lines, and investigated the effect of MsrB1 knockdown on CRC phenotypes and possible mechanisms involved in. The results showed that MsrB1 was highly expressed in both CRC tissues and cell lines, and that cell proliferation, migration and invasion were significantly inhibited, but apoptosis was increased after MsrB1 knockdown in colorectal cancer HCT116 and RKO cell lines, compared to control siRNA group. In addition, E-cadherin protein level was increased, vimentin and Snail protein were greatly decreased after knockdown of MsrB1 in cells. Furthermore, pGSK-3β (Ser9) and β-catenin protein levels were reduced, the promoter activity of TCF/LEF construction was inhibited after MsrB1 knockdown in cells, suggesting that GSK-3β/β-catenin signaling axis was involved in the tumorigenesis of CRC. In conclusion, the oncogenic role and related mechanisms of MsrB1 in CRC discovered in our work determined the potential role of MsrB1 as a biomarker and may provide a new target for clinical therapy of CRC.
甲硫氨酸亚砜还原酶 B1(MsrB1)可以催化游离和蛋白结合的 R-甲硫氨酸亚砜(R-MetO)转化为甲硫氨酸(Met)。据报道,MsrB1 在肝癌和人类骨肉瘤的发生发展中起着重要作用。然而,关于 MsrB1 在人结直肠癌(CRC)中的作用知之甚少。本研究检测了 CRC 组织和细胞系中 MsrB1 的表达水平,并研究了 MsrB1 敲低对 CRC 表型的影响及其可能涉及的机制。结果表明,MsrB1 在 CRC 组织和细胞系中均高表达,与对照 siRNA 组相比,MsrB1 敲低后结肠癌细胞 HCT116 和 RKO 细胞的增殖、迁移和侵袭明显受到抑制,但凋亡增加。此外,细胞中 MsrB1 敲低后 E-钙黏蛋白蛋白水平升高,波形蛋白和 Snail 蛋白大大减少。此外,细胞中 MsrB1 敲低后 pGSK-3β(Ser9)和β-连环蛋白蛋白水平降低,TCF/LEF 构建体的启动子活性受到抑制,表明 GSK-3β/β-连环蛋白信号通路参与了 CRC 的发生。综上所述,本研究发现 MsrB1 在 CRC 中的致癌作用及其相关机制,确定了 MsrB1 作为生物标志物的潜在作用,并可能为 CRC 的临床治疗提供新的靶点。