MND1 protein mediates DNA damage repair and is a promising novel therapeutic target in hepatocellular carcinoma

Abstract

Background and aims: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, highlighting the urgent need to identify novel therapeutic targets. Bioinformatic analysis initially identified meiotic nuclear division 1 (MND1) as a differentially expressed gene in HCC, with significant associations to DNA damage repair pathways, suggesting its potential functional relevance in hepatocarcinogenesis. Based on these findings, this study aims to systematically characterize the expression profile of MND1 in HCC and to further elucidate its biological functions as well as the underlying molecular mechanisms driving HCC progression.

Methods: The expression profile of MND1 was validated using data from public databases along with 22 paired clinical HCC specimens. The functional roles of MND1 were investigated through in vitro assays (CCK-8, Transwell, and flow cytometry) and in vivo subcutaneous/orthotopic xenograft mouse models. Mechanistically, co-immunoprecipitation (Co-IP) coupled with mass spectrometry, immunofluorescence, and rescue experiments were applied to identify interacting proteins and to elucidate the underlying molecular pathways.

Results: Multi-omics analysis and clinical validation revealed that MND1 is overexpressed in HCC tissues and significantly correlates with poor prognosis. Comprehensive in vitro and in vivo functional studies further demonstrated that MND1 drives HCC progression by regulating tumor cell proliferation, migration, and invasion. Mechanistically, we uncovered a close functional association between MND1 and TRIM28, which promotes genomic instability by enhancing the activity of the DNA damage response (DDR) pathway.

Conclusions: These findings suggest that MND1 may serve as both a potential molecular marker and an oncogenic contributor in HCC. Importantly, the newly identified MND1–TRIM28–DDR regulatory axis offers a promising rationale for the development of targeted therapeutic strategies.

Keywords

Hepatocellular carcinoma (HCC) / Meiotic nuclear division 1 (MND1) / Tripartite motif-containing 28 (TRIM28) / DNA damage repair / Therapeutic target

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