HNRNPA2B1 as an emerging coordinator of RNA fate in cancer: m6A reading, RNA export, translation reprogramming, and immune–metabolic adaptation

Cancer progression and treatment failure are increasingly recognized as consequences of tumor plasticity rather than static genetic alterations. A key component of this plasticity is the ability of cancer cells to reprogram RNA fate, thereby reshaping gene expression outputs in response to microenvironmental stress, immune surveillance, infection, and therapeutic pressure. Among RNA-binding proteins involved in post-transcriptional regulation, heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) has been increasingly implicated in several cancer-associated RNA regulatory processes that extend beyond its initial characterization as an N6-methyladenosine (m6A) reader. In this review, we synthesize recent studies showing that HNRNPA2B1 participates in multiple aspects of RNA regulation, including m6A-dependent stabilization of oncogenic lncRNAs and mRNAs, ISGylation-associated selective nuclear export of m6A-tagged transcripts, cytoplasmic translation control, and extracellular vesicle-mediated RNA communication. We further discuss studies associating HNRNPA2B1 with immune-metabolic phenotypes and therapy response, including tumor acidosis, ferroptosis-related pathways, immune evasion, and altered sensitivity to chemotherapy, radiotherapy, endocrine therapy, and targeted treatments. Importantly, these mechanisms have largely been described in distinct tumor types, experimental systems, and biological contexts, and therefore should not yet be interpreted as a single universally established regulatory cascade. Instead, we organize current evidence within a context-aware framework in which HNRNPA2B1 is discussed as a possible regulator of selected RNA fate modules rather than as an established pan-cancer RNA fate hub. By distinguishing experimentally supported mechanisms from hypothesis-generating interpretations, this review provides a balanced assessment of the current evidence, limitations, and therapeutic implications of HNRNPA2B1-related RNA regulation in cancer.