Immune escape of multiple myeloma cells results from low miR29b and the ensuing epigenetic silencing of proteasome genes.

ABSTRACT:

Background

Activation of CD28 on multiple myeloma (MM) plasma cells, by binding to CD80 and CD86 on dendritic cells, decreases proteasome subunit expression in the tumor cells and thereby helps them evade being killed by CD8⁺ T cells. Understanding how CD28 activation leads to proteasome subunit downregulation is needed to design new MM therapies.

Methods

This study investigates the molecular pathway downstream of CD28 activation, using an in vitro model consisting of myeloma cell lines stimulated with anti-CD28-coated beads.

Results

We show that CD28 engagement on U266 and RPMI 8226 cells activates the PI3K/AKT pathway, reduces miR29b expression, increases the expression of DNA methyltransferase 3B (DNMT3B, a target of miR29b), and decreases immunoproteaso

SUBMITTER: Leone P 

PROVIDER: S-EPMC11040965 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature