Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma.

ABSTRACT:

Background

The dysregulation of the DNA damage response (DDR) plays a vital role in cancer development and inadequate response to anti-cancer therapy. We investigated the involvement of DNA polymerase theta (Polθ), the principal component of the microhomology-mediated end joining (MMEJ) pathway, in the pathogenesis of multiple myeloma (MM).

Methods

We explored the expression levels of Polθ and assessed its prognostic relevance in a cohort of 124 MM patients at our institution. We demonstrated the impacts of Polθ inhibition on genomic stability and cell viability in MM using shRNA and a pharmacological inhibitor. To elucidate the role of Polθ-mediated MMEJ in repairing melphalan-induced DNA damage, we employed Western blot and EJ2-GFP reporter assay to evaluate the activation

SUBMITTER: Li Q 

PROVIDER: S-EPMC12513101 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature