LAUSR

c-Myc and E2F1 play critical roles in many human cancers. As long non-coding RNAs (lncRNA) are known to regulate various tumorigenic processes, elucidation of mechanisms of crosstalk between lncRNAs and c-Myc/E2F1-related signaling pathways could provide important insights into cancer biology. In this study, we used integrated bioinformatic analyses and found that the lncRNA MNX1-AS1 is upregulated in non-small cell lung cancer (NSCLC) via copy number gain and c-Myc-mediated transcriptional activation. High levels of MNX1-AS1 were associated with poor clinical outcomes in lung cancer patients. MNX1-AS1 promoted cell proliferation and colony formation in vitro and tumor growth in vivo. MNX1-AS1 bound and drove phase separation of IGF2BP1, which increased the interaction of IGF2BP1 with the 3'-UTR of c-Myc and E2F1 mRNA to promote their stability. The c-Myc/MNX1-AS1/IGF2BP1 positive feedback loop accelerated cell cycle progression and promoted continuous proliferation of lung cancer cells. In a lung cancer patient-derived xenograft model, inhibition of MNX1-AS1 suppressed cancer cell proliferation and tumor growth. These findings offer new insights into the regulation and function of c-Myc and E2F1 signaling in NSCLC tumorigenesis and suggest that the MNX1-AS1/IGF2BP1 axis may serve as a potential biomarker and therapeutic target in NSCLC.