piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer.

Abstract

Conventional targeted therapies primarily rely on small molecules and proteins. However, they often struggle to enter specific protein conformations, which limits their therapeutic effectiveness. In contrast, RNA therapy is emerging as a more precise and effective targeting strategy. Through differential analysis comparing Pandora-Seq data with clinical samples, we discovered that the small RNA piR-28846 naturally, occurring in human body, exhibited low expression levels in ovarian cancer tissues. Experimental results indicate that piR-28846 inhibits the growth of ovarian cancer cells. Additionally, piR-28846 demonstrated significant therapeutic effects in xenograft models and ovarian cancer-like organoids. Further studies revealed that piR-28846 binds to NSUN2 and down-regulates it, which in turn affects the stability of KPNA2 mRNA. Notably, KPNA2 negatively regulates NSUN2 expression and localization. Given its inhibitory effects observed in vivo, in vitro, and in the ovarian cancer organoid model, we believe piR-28846 has strong potential as a small nucleic acid therapy of ovarian cancer.