Full-Length Transcriptome Profiles Reveal the Molecular Function of Oncogene HNRNPA2B1 in Triple-Negative Breast...

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with the worst prognosis. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), a member of the RNA-binding protein (RBP) hnRNPs family, is aberrantly expressed in various human cancers, serving as a marker of poor prognosis and acting as an oncogene. However, its expression, biological function, and molecular mechanism in TNBC remain unclear. In this study, we examined the expression of HNRNPA2B1 in one normal mammary epithelial cell line (MCF10A) and four TNBC cell lines (HS 578 T, BT-20, MDA-MB-468, and MDA-MB-231). We conducted in vitro and in vivo knockdown experiments to compare the growth ability, gene expression profiles, and alternative splicing patterns of TNBC cells with HNRNPA2B1 knockdown to those of control cells. Our results demonstrated that HNRNPA2B1 is overexpressed in triple-negative breast cancer tissues and cell lines. Knockdown of HNRNPA2B1 significantly inhibited proliferation and metastasis while promoting apoptosis in TNBC cells. Mechanistically, HNRNPA2B1 knockdown broadly impacted the expression and alternative splicing of genes associated with cell migration, proliferation, and apoptosis. Using Nanopore long-read sequencing, we further revealed that HNRNPA2B1 regulates gene expression in TNBC cells through the modulation of alternative polyadenylation. These findings highlight the critical role of HNRNPA2B1 in TNBC progression, providing new insights into its mechanisms and potential therapeutic applications.