The interplay between non-coding RNAs and Wnt signaling pathway in leukemia: A narrative review

Leukemias are heterogeneous hematologic malignancies that involve dysregulated proliferation and impaired differentiation of hematopoietic cells. The Wnt signaling pathway, which regulates hematopoietic stem cell self-renewal and lineage commitment, is dysregulated across leukemia subtypes. Non-coding RNAs (ncRNAs), which include microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs, have been identified as important post-transcriptional and epigenetic regulators of oncogenic signaling networks. There is growing evidence for a complex, bidirectional relationship between ncRNAs and the Wnt/β-catenin pathway, but this has not yet been summarized or integrated into the context of leukemia. This study examines how ncRNA manipulation of core Wnt components – β-catenin, Frizzled receptors, and Dvl (dishevelled) proteins – affect leukemic cell survival, proliferation, stemness, and treatment resistance. Furthermore, we discuss reciprocal regulation, in which Wnt stimulation affects ncRNA production, forming feed-forward loops that promote leukemogenesis. By synthesizing disparate findings from studies investigating ncRNA and Wnt signaling mechanisms across leukemia subtypes, we identify critical mechanistic gaps in the literature, as well as opportunities and controversies that could be that could be leveraged in evaluating ncRNA–Wnt interactions as diagnostic and therapeutic targets. This review presents a comprehensive study integrating ncRNA biology and Wnt-driven leukemic development in order to identify crucial insights into disease vulnerabilities and future research initiatives.