Mucosa-associated lymphoma antigen 1 (MALT1) is an oncogene in diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma subsets. However, the role of MALT1 in various cancers, particularly prostate cancer, remains poorly understood. This study demonstrates that MALT1 overexpression is significantly associated with mismatch repair (MMR) gene mutation levels and significantly promotes prostate cancer cell proliferation and clonogenicity both in vivo and in vitro, while reducing apoptosis. MALT1 expression is closely associated with immune checkpoint genes, tumor mutational burden (TMB), and microsatellite instability (MSI) in most cancers. Gene ontology (GO) analysis reveals that co-expressed MALT1 genes are involved in heterocellular adhesion, actin filament-mediated motility regulation, and action potential regulation. Gene set enrichment analysis (GSEA) revealed that MALT1 expression is associated with multiple signaling pathways in prostate cancer, including the NF-κB signaling pathway, the Wnt/β-catenin signaling pathway, and the TGF-β signaling pathway. Furthermore, MALT1 expression was significantly associated with the infiltration of immune cells (including B cells, CD8+ T cells, dendritic cells, and macrophages), but negatively correlated with the infiltration of CD4+ cells in prostate cancer. Therefore, MALT1 may be an emerging therapeutic target for various cancers, especially prostate cancer.
Researchers used Matrigel-coated Transwell chambers to assess tumor invasiveness. Cells that degraded Matrigel and crossed the membrane were counted, and the results showed that the number of invasive PC-3 cells in the MALT1 knockdown cell group was lower than that in the control group. Similar results were obtained for LNCaP cells (Figure 1A). To assess whether downregulation of MALT1 expression affected the metastatic ability of PC-3 and LNCaP cells, they performed Transwell experiments. The results showed that the migration ability of MALT1 knockdown cells was significantly reduced (Figure 1B).
Figure 1. Downregulation of MALT1 inhibited the migration and invasion of PCa cells. (Tan H, et al., 2021)