PLAGL2 Promotes the Proliferation and Migration of Diffuse Large B-cell Lymphoma Cells via Wnt/β-catenin Pathway

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 in vivo tumor growth of DLBCL.

In conclusion, PLAGL2 promoted the malignancy of DLBCL through activation of Wnt/β-catenin pathway.