Abnormal translation of the MYC proto-oncogene is a hallmark of the initiation and maintenance of tumorigenesis. However, the molecular mechanism underlying increased MYC protein levels in certain cancer types without a corresponding increase in MYC mRNA levels is unclear. Here, we identified a novel lncRNA, MTAR1, which is critical for post-transcriptional regulation of MYC-induced tumorigenesis. MTAR1 is essential for recruiting IGF2BPs into PABP1-mediated liquid–liquid phase separation (LLPS) complexes and facilitates IGF2BPs-mediated MYC mRNA translation. MTAR1 enhanced binding between IGF2BPs and PABP1, thereby promoting MYC mRNA stability and increased MYC mRNA translation. In summary, MTAR1 is a novel MYC-related lncRNA that contributes to tumor progression by enhancing MYC translation through mediating PABP1/IGF2BPs liquid–liquid phase separation.
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We thank Dr. Kyle Vaughn Laster for editing this manuscript. We thank Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac) and professor Andrew Dingley, for editing this manuscript. We thank BioRender.com for their software that enabled us to generate the graphic abstract.
This research is supported by the National Natural Science Foundations of China (No. 81802876), the Project of Science and Technology of the Henan Province for Tackling Key Problems (182102310128) and the National Natural Science Foundations of China (Nos. 81872335, 81802875, 81972639).
The authors declare no competing interests.
Ethics approval and consent to participate
Tumor and adjacent ESCC tissues were obtained from ESCC cancer patients who underwent surgery at Henan Cancer Hospital. The experimental protocol was approved by the ethics committee of Zhengzhou University School of Medicine, Henan Cancer Hospital (No. 2017407). No patient received chemotherapy or radiotherapy prior to surgery. Animal experimental protocol was approved by the ethics committee of China-US (Henan) Hormel Cancer Institute (No. CUHCI2019003).
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Gao, Y., Jiang, M., Guo, F. et al. A novel lncRNA MTAR1 promotes cancer development through IGF2BPs mediated post-transcriptional regulation of c-MYC. Oncogene 41, 4736–4753 (2022). https://doi.org/10.1038/s41388-022-02464-x