TIMD4 通过 Wnt/β-catenin 通路调节弥漫大 B 细胞淋巴瘤细胞的增殖和凋亡。

TIMD4 exhibits regulatory capability on the proliferation and apoptosis of diffuse large B-cell lymphoma cells via the Wnt/β-catenin pathway.

机构信息

Department of Pharmacy of Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Department of Rheumatology of Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

出版信息

J Gene Med. 2020 Aug;22(8):e3186. doi: 10.1002/jgm.3186. Epub 2020 Mar 26.

DOI:10.1002/jgm.3186

PMID:32187802

Abstract

BACKGROUND

Prior studies have noted the importance of T cell immunoglobulin and mucin domain containing 4 (TIMD4) in various diseases and its functions on cell malignant behaviors. However, the biological function of TIMD4 in diffuse large B-cell lymphoma (DLBCL) is unknown.

METHODS

Relative expression of TIMD4 was analyzed based on the GSE56315 array including 88 cases of human tissues. TIMD4 expression in cells was detected using a quantitative reverse transcriptase-polymerase chain reaction and western blot experiments. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay and apoptotic properties were assessed through the detection of related proteins by western blotting. The underlying molecular mechanism of TIMD4 in DLBCL was predicted and confirmed using KEGG enrichment analysis and western blotting.

RESULTS

The results indicate that TIMD4 is overexpressed in DLBCL tissues and the poor prognosis of DLBCL patients is significantly linked with the higher TIMD4 expression. The loss-of-TIMD4 experiment in CYP6D reveals that knockdown of TIMD4 blocks cell growth and accelerates cell apoptosis, whereas the gain-of-TIMD4 experiment in Raji cells suggests that up-regulation of TIMD4 promotes cell proliferation and inhibits cell apoptosis. The activity of the Wnt/β-catenin pathway is mediated by the TIMD4 expression in DLBCL cells.

CONCLUSIONS

These findings demonstrate that TIMD4 is up-regulated in patients with DLBCL and the regulatory effects of TIMD4 on cell proliferation and apoptosis are associated with the Wnt/β-catenin pathway, posing a novel target for DLBCL therapy.

摘要

背景

先前的研究已经注意到 T 细胞免疫球蛋白和粘蛋白结构域 4（TIMD4）在各种疾病中的重要性及其对细胞恶性行为的功能。然而，TIMD4 在弥漫性大 B 细胞淋巴瘤（DLBCL）中的生物学功能尚不清楚。

方法

基于包括 88 个人体组织的 GSE56315 数组分析 TIMD4 的相对表达。使用定量逆转录-聚合酶链反应和 Western blot 实验检测细胞中的 TIMD4 表达。使用细胞计数试剂盒-8（CCK-8）测定法测量细胞增殖，并通过 Western blot 检测相关蛋白来评估凋亡特性。使用 KEGG 富集分析和 Western blot 预测和验证 TIMD4 在 DLBCL 中的潜在分子机制。

结果

结果表明，TIMD4 在 DLBCL 组织中过表达，DLBCL 患者的不良预后与 TIMD4 表达水平较高显著相关。在 CYP6D 中进行 TIMD4 缺失实验表明，下调 TIMD4 可阻断细胞生长并加速细胞凋亡，而在 Raji 细胞中进行 TIMD4 上调实验表明，上调 TIMD4 可促进细胞增殖并抑制细胞凋亡。Wnt/β-catenin 通路的活性由 DLBCL 细胞中的 TIMD4 表达介导。