The Emerging Role of Histone Methyltransferase ASH1L in Tumor Development

Histone modifications play a fundamental role in epigenetic regulation. Histone methylation mediated by enzymes like absent, small, or homeotic discs 1-like (ASH1L) has emerged as a critical process in normal cellular function and disease, particularly cancer. ASH1L, a member of the Trithorax-group (TrxG) protein family, acts as a histone methyltransferase with the ability to establish H3K36 dimethylation (H3K36me2). In recent years, an increasing number of studies have focused on the dysregulation of ASH1L in various tumors and its potential as a therapeutic target. A detailed literature survey was conducted to compile data from PubMed, SciFinder, and ScienceDirect. After screening, data extraction, and descriptive analysis, a series of related articles was retained. This comprehensive review systematically dissects the molecular mechanisms by which ASH1L modulates oncogenic processes in these cancers, emphasizing its roles in transcriptional activation of driver genes, epigenetic reprogramming, cell cycle progression, and maintenance of cancer stem cell properties. Additionally, we summarize current progress in targeting ASH1L for cancer therapy, highlighting challenges and future directions. ASH1L, as a histone methyltransferase, is associated with the tumor microenvironment, and its anti-tumor targeted therapies require further exploration in the future.