HEN methyltransferase 1 (HENMT1) is an RNA methyltransferase that catalyzes 2′-O-methylation of P-element-induced wimpy testis (PlWI)-interacting RNAs (piRNAs) within the small RNA silencing pathway and methylates microRNAs (miRNAs). By stabilizing these RNA molecules, HENMT1 plays a pivotal role in regulating the biological processes that they target, thereby maintaining cellular homeostasis. Mutations in HENMT1 homologs across various species have been shown to alter biological traits and impair reproduction. HENMT1 mutations have been linked to infertility and tumor development in humans. This comprehensive review first introduces the structure and function of HENMT1 and its homologs, with a focus on elucidating the piRNA methylation process. Next, we examine the aberrant expression of HENMT1 in human cancers and its relationship with immune infiltration by analyzing the Cancer Genome Atlas (TCGA) database and tumor immune infiltration profiling, providing insights into the dysregulation of HENMT1 in diseases such as infertility and cancer. Finally, we discuss current knowledge and future perspectives on HENMT1’s function in cancer progression.
Jiang et al. (2026) studied this question.