MPDZ is associated with immune infiltration and regulates migration and invasion by switching YAP1 phosphorylation in colorectal cancer

Multiple PDZ Domain Crumbs Cell Polarity Complex Component (MPDZ) is involved in a few human cancers. However, the features and potential mechanisms of MPDZ in progression of colorectal cancer (CRC) remains unknown. In TCGA and GEO cohorts, the prognostic role of MPDZ in CRC was determined by the Kaplan-Meier method and univariate regression analysis. GSEA for KEGG, Hallmark and GO were performed to characterize crucial pathways that MPDZ was involved. Immune infiltration and immunotherapeutic outcome were evaluated by calculating TCGA and GEO data. CCK8, EDU, transwell and wound healing assay were used to assess the influence of MPDZ on pernicious performance of CRC cell. CD8+ T cells and CRC cells were co-cultured to explore the effect of MPDZ on the tumor microenvironment. qRT–PCR, western blot, immunoprecipitation (IP) and methylated RNA immunoprecipitation (me-RIP) were implemented in seeking for the potential mechanisms of MPDZ in CRC. CRC patients with elevated MPDZ expression suffered from significantly worse prognosis. Simultaneously, MPDZ could be an independent prognostic risk indicator in CRC. GSEA analysis revealed that MPDZ involved in pathways related to metastasis and cell cycle in CRC. In addition, MPDZ expression were related to several immunoinhibitors and had the ability to predict immunotherapy response. Finally, in vitro assays demonstrated that MPDZ knockdown inhibited migration, invasion and immune evasion of CRC cell. Mechanistically, MPDZ knockdown enhanced YAP1 phosphorylation by increased LATS1 expression to inhibit epithelial mesenchymal transition (EMT) and immune evasion of CRC cell. Moreover, m6A-MPDZ mRNA may be recognized and degraded by m6A recognition protein YTHDF2. MPDZ was critical for CRC development and could be a promising candidate for combination therapy for immunotherapy of CRC patients.