Data from MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc–Mediated Cell-Cycle Progression and Proliferation in Lung Cancer Article Swipe

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Qingqing Zhu , Chongguo Zhang , Tianyu Qu , Xiyi Lu , Xuezhi He , Wei Li , Dandan Yin , Liang Han , Renhua Guo , Erbao Zhang ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1158/0008-5472.c.6514268

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.Significance: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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Cancer research Cell cycle Cell growth Biology Cell cycle progression Lung cancer Genetics Oncology Cancer Medicine

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/0008-5472.c.6514268
OA Status: gold
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DOI: https://doi.org/10.1158/0008-5472.c.6514268

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Title: Data 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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Type: preprint

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Language: en

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Publication year: 2024

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Publication date: 2024-03-12

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Authors: Qingqing Zhu, Chongguo Zhang, Tianyu Qu, Xiyi Lu, Xuezhi He, Wei Li, Dandan Yin, Liang Han, Renhua Guo, Erbao Zhang

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Landing page: https://doi.org/10.1158/0008-5472.c.6514268

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Concepts: Cancer research, Cell cycle, Cell growth, Biology, Cell cycle progression, Lung cancer, Genetics, Oncology, Cancer, Medicine

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