PRUNE1-IGF2BP3 Forms a Positive Feedback Loop By Stabilizing SOX4 mRNA in an m6A-Denpendent Manner to Promote Multiple Myeloma with 1q21 Gain

Multiple myeloma (MM) with chromosome 1q21 Gain is a group of fatal malignancies characterized by high heterogeneity. Our previous findings have indicated that PRUNE1 (located on chromosome 1q21.3) promotes MM by enhancing the connections between purine and mitochondrion. In this study we have discovered that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) acts downstream of PRUNE1 and is highly expressed in MM with 1q21 Gain, showing a clinical correlation with distant overall survival. To investigate the impact of IGF2BP3 on cellular proliferation, migration, and apoptosis, we conducted CCK-8 assays, transwell assays, and flow cytometry assays, respectively. Mechanistically, IGF2BP3 enhances the stability of SOX4, a transcription factor of PRUNE1, in an m6A dependent manner. This creates a positive feedback loop that promotes MM cell proliferation and invasion through enhanced glycolysis. These findings shed light into the regulatory network of SOX4/PRUNE1/IGF2BP3 among MM with 1q21 Gain and provide rationale for targeting the m6A machinery in the treatment.

No relevant conflicts of interest to declare.