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MIF/SCL3A2 耗竭通过 AKT/GSK-3β 通路和细胞铁死亡抑制结直肠癌细胞的增殖和转移。

MIF/SCL3A2 depletion inhibits the proliferation and metastasis of colorectal cancer cells via the AKT/GSK-3β pathway and cell iron death.

机构信息

Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Department of Pathology, Shenzhen Longgang Central Hospital, Shenzhen, China.

出版信息

J Cell Mol Med. 2022 Jun;26(12):3410-3422. doi: 10.1111/jcmm.17352. Epub 2022 May 13.

DOI:10.1111/jcmm.17352
PMID:35567291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9189354/
Abstract

This study investigated the mechanisms of migration inhibitory factor (MIF) and solute carrier family 3 member 2 (SLC3A2) in colorectal cancer progression. The levels of MIF and SLC3A2 expression in cells were measured by RT-qPCR. SW480 and SW620 cells were transfected with sh-MIF and sh-SLC3A2, respectively. MIF, SLC3A2, GPX4, E-cadherin and N-cadherin expression were detected by immunofluorescence (IF). CCK8 and Transwell assays were performed to detect cell proliferation and migration. Co-immunoprecipitation (CoIP) was used to measure the binding activity of MIF and SLC3A2. Finally, a nude mouse tumorigenicity assay was used to confirm the functions of MIF and SLC3A2 in colorectal cancer. Results showed that the levels of MIF and SLC3A2 expression were up-regulated in colorectal cancer cells. Inhibition of MIF or SLC3A2 expression prevented cell proliferation, migration, epithelial-mesenchymal transition (EMT) and invasion. In addition, knockdown of MIF and SLC3A2 promoted iron death in SW480 and SW620 cells. CoIP results showed that MIF and SLC3A2 directly interact with each other. Knockdown of both MIF and SLC3A2 inhibited tumour growth and metastasis via the AKT/GSK-3β pathway in vivo. The Akt/GSK-3β pathway was found to participate in regulating MIF and SLC3A2 both in vivo and in vitro. MIF and SLC3A2 might be potential biomarkers for monitoring the treatment of colorectal cancer.

摘要

本研究探讨了迁移抑制因子(MIF)和溶质载体家族 3 成员 2(SLC3A2)在结直肠癌进展中的作用机制。采用 RT-qPCR 检测细胞中 MIF 和 SLC3A2 表达水平。分别用 sh-MIF 和 sh-SLC3A2 转染 SW480 和 SW620 细胞。采用免疫荧光(IF)检测 MIF、SLC3A2、GPX4、E-钙黏蛋白和 N-钙黏蛋白的表达。通过 CCK8 和 Transwell 实验检测细胞增殖和迁移。采用 co-immunoprecipitation(CoIP)检测 MIF 和 SLC3A2 的结合活性。最后,通过裸鼠肿瘤生成实验证实 MIF 和 SLC3A2 在结直肠癌中的作用。结果表明,结直肠癌细胞中 MIF 和 SLC3A2 的表达水平上调。抑制 MIF 或 SLC3A2 的表达可阻止细胞增殖、迁移、上皮-间充质转化(EMT)和侵袭。此外,下调 MIF 和 SLC3A2 可促进 SW480 和 SW620 细胞铁死亡。CoIP 结果表明,MIF 和 SLC3A2 直接相互作用。体内敲低 MIF 和 SLC3A2 通过 AKT/GSK-3β 通路抑制肿瘤生长和转移。体内外研究均发现 Akt/GSK-3β 通路参与调节 MIF 和 SLC3A2。MIF 和 SLC3A2 可能是监测结直肠癌治疗的潜在生物标志物。

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