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Supplementary Movie S1 from MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc–Mediated Cell-Cycle Progression and Proliferation in Lung Cancer

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posted on 2023-03-31, 05:43 authored by Qingqing Zhu, Chongguo Zhang, Tianyu Qu, Xiyi Lu, Xuezhi He, Wei Li, Dandan Yin, Liang Han, Renhua Guo, Erbao Zhang

The quick rearrangement of IGF2BP1 droplets. A time-lapse movie of droplets formed by IGF2BP1 undergoes a fusion event.

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National Natural Science Foundation of China (NSFC)

Jiangsu province science and technology project

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ARTICLE ABSTRACT

c-Myc and E2F1 play critical roles in many human cancers. As long noncoding RNAs (lncRNA) are known to regulate various tumorigenic processes, elucidation of mechanisms of cross-talk 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 patients with lung cancer. 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 (untranslated region) 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. MNX1-AS1 drives phase separation of IGF2BP1 to increase c-Myc and E2F1 signaling and to activate cell-cycle progression to promote proliferation in NSCLC.

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