Department of Hematology and Lishui City People's Hospital (the Sixth Affiliated Hospital of Wenzhou Medical University), Lishui, Zhejiang Province, China.
Department of Oncology, Lishui City People's Hospital (the Sixth Affiliated Hospital of Wenzhou Medical University), Lishui, Zhejiang Province, China
Ann Clin Lab Sci. 2022 May;52(3):359-366.
Pleomorphic adenoma gene like-2 (PLAGL2) belongs to PLAG protein family and functions as a zinc finger transcriptional factor to participate in the cellular processes, including cell transformation, migration, and apoptosis. Increasing evidence has shown the oncogenic role of PLAGL2 in various cancers, while the potential molecular mechanism and biology roles of PLAGL2 in diffuse large B-cell lymphoma (DLBCL) are still unclear.
Expression of PLAGL2 was found to be elevated in DLBCL cells. Functional assays showed that silence of PLAGL2 suppressed cell proliferation and reduced the cell migration and invasion in DLBCL. The cell proliferation and metastasis in DLBCL were promoted by over-expression of PLAGL2. Moreover, the protein expression of E-cadherin was increased, while the protein expressions of N-cadherin and vimentin were decreased in DLBCL cells by knockdown of PLAGL2. However, over-expression of PLAGL2 promoted epithelial to mesenchymal transition (EMT) of DLBCL through down-regulation of E-cadherin, and up-regulations of N-cadherin and vimentin.
Over-expression of PLAGL2 up-regulated β-catenin and c-myc, while down-regulated axis inhibition protein 2 (AXIN2) and adenomatous polyposis coli (APC) in DLBCL. Knockdown of PLAGL2 suppressed the activation of Wnt/β-catenin pathway in DLBCL through downregulating β-catenin and c-myc but upregulating AXIN2 and APC. Xenograft model also demonstrated that interference of PLAGL2 repressed the tumor growth of DLBCL.
In conclusion, PLAGL2 promoted the malignancy of DLBCL through activation of Wnt/β-catenin pathway.
多形性腺瘤基因样 2（PLAGL2）属于 PLAG 蛋白家族，作为锌指转录因子发挥作用，参与细胞转化、迁移和凋亡等细胞过程。越来越多的证据表明，PLAGL2 在多种癌症中具有致癌作用，而 PLAGL2 在弥漫性大 B 细胞淋巴瘤（DLBCL）中的潜在分子机制和生物学作用尚不清楚。
发现 PLAGL2 在 DLBCL 细胞中表达升高。功能分析表明，沉默 PLAGL2 可抑制细胞增殖，并降低 DLBCL 中的细胞迁移和侵袭。而过表达 PLAGL2 则促进了 DLBCL 细胞的增殖和转移。此外，PLAGL2 敲低可增加 E-钙黏蛋白的蛋白表达，同时降低 N-钙黏蛋白和波形蛋白的蛋白表达，从而抑制 DLBCL 细胞的上皮间质转化（EMT）。然而，过表达 PLAGL2 通过下调 E-钙黏蛋白，并上调 N-钙黏蛋白和波形蛋白，促进了 DLBCL 的 EMT。
过表达 PLAGL2 上调了β-catenin 和 c-myc，而下调了轴抑制蛋白 2（AXIN2）和结肠腺瘤性息肉病基因（APC）在 DLBCL 中的表达。PLAGL2 敲低通过下调β-catenin 和 c-myc 而抑制了 Wnt/β-catenin 通路在 DLBCL 中的激活，同时上调了 AXIN2 和 APC。异种移植模型也表明，PLAGL2 的干扰抑制了 DLBCL 的肿瘤生长。
总之，PLAGL2 通过激活 Wnt/β-catenin 通路促进了 DLBCL 的恶性转化。
