The regulation loop of MARVELD1 interacting with PARP1 in DNA damage response maintains genome stability and promotes therapy resistance of cancer cells

Abstract

The DNA damage response (DDR) plays crucial roles in cancer prevention and therapy. Poly(ADP-ribose) polymerase 1 (PARP1) mediates multiple signal transduction in the DDR as a master regulator. Uncovering the regulatory factors of PARP1 contributes to a more comprehensive view of tumorigenesis and treatment strategies. Here, we reveal that MARVELD1 acts as a mediator of DDR to perform early events and maintain genome stability. Mechanistically, PARP1 PARylates MARVELD1 at D102, D118 and D130, and in turn, MARVELD1 stabilizes PARP1 by enhancing NAA50-mediated acetylation, thus forming a positive feedback loop. MARVELD1 knockout mice and their embryo fibroblasts exhibit genomic instability and shorter half-life of PARP1. Moreover, MARVELD1 partnering with PARP1 facilitates resistance to genotoxic drugs and disrupts PARP inhibitor (PARPi) effect in PDX model of colorectal cancer (CRC). Overall, our results underline the link between MARVELD1 and PARP1 in therapeutic resistance based on DDR and provide new insights for clinical tumor therapy of PARPi.

Machine learning visceral obesity-related genes based on MARVELD1 model for predicting the prognosis and immune cell infiltration of ovarian cancer

“…MARVELD1, a member of the MARVEL domain-containing protein family, exhibits tumor suppressor activity in breast, cervical, prostate, hepatocellular, and other cancers (34)(35)(36). Previously, a basic study demonstrated MARVELD1's role in inducing resistance to 5-FU combined with olaparib in colorectal cancer (37). yet its function in ovarian cancer has remained underexplored.…”

Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4+ and CD8+T Lymphocytes in Clear Cell Renal Cell Carcinoma

“…Staining was visualized with DAB and hematoxylin counterstaining. For semi-quantitative analysis, two pathologists independently evaluated the stained sections according to evaluation standards on a 12-point scale by calculating the immunoreactivity score [ 62 ]. For IHC staining of mice tumor tissues following standardized procedures, the primary antibodies used were anti-CD4 (67786-1-lg, Proteintech) and anti-CD8 (29896-1-AP, Proteintech).…”