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

Abstract

Background: 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.

Methods: The prognostic role of MPDZ in CRC was determined by Kaplan-Meier and univariate regression analysis. Enrichment analysis was performed to characterize crucial pathways of MPDZ. Immune infiltration and immunotherapeutic outcome were further evaluated. CCK8, EDU, transwell, and wound healing assay were used to assess the influence of MPDZ on pernicious performance of CRC cells. 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.

Results: CRC patients with elevated MPDZ expression suffered from significantly worse prognosis. Enrichment 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 cells. Mechanistically, MPDZ knockdown enhanced YAP1 phosphorylation by increased LATS1 expression. Moreover, m6A-MPDZ mRNA may be recognized and degraded by m6A recognition protein YTHDF2.

Conclusions: MPDZ was critical for CRC development and could be a promising candidate for the treatment of CRC patients.

Keywords: Colorectal cancer; Immune infiltration; Invasion; MPDZ; Migration.