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c-Myc-induced long noncoding RNA MIRE cooperates with hnRNPK to stabilize ELF2 mRNA and promotes clear cell renal cell carcinogenesis

Cancer Gene Therapy volume 30, pages 1215–1226 (2023)Cite this article

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Abstract

Elevated expression of c-Myc is associated with a variety of human cancers including clear cell renal cell carcinoma (ccRCC). Increasing evidence suggests that long noncoding RNAs (lncRNAs) are an important class of molecules that regulate both tumor initiation and progression. Here, we report the lncRNA c-Myc-induced regulator of ELF2 (MIRE) as a transcriptional target of c-Myc. MIRE functions as an oncogenic molecule in ccRCC by increasing ELF2 expression. Mechanistically, MIRE promotes phase separation of the RNA binding protein hnRNPK and facilitates the binding of hnRNPK to ELF2 mRNA, thereby resulting in the stabilization of ELF2 mRNA. Interestingly, MIRE is also under transcriptional control by ELF2, establishing an ELF2-MIRE positive feedback loop. Together, these findings provide new insights into the mechanisms by which c-Myc promotes tumorigenesis. They also implicate MIRE as an important regulator of ccRCC carcinogenesis.

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Fig. 1: MIRE functions as an oncogenic lncRNA in clear cell renal cell carcinoma (ccRCC).
Fig. 2: MIRE is transcriptionally up-regulated by c-Myc.
Fig. 3: MIRE increases ELF2 expression.
Fig. 4: MIRE exerts its oncogenic role by increasing ELF2 expression.
Fig. 5: MIRE cooperates with hnRNPK to enhance ELF2 mRNA stability.
Fig. 6: MIRE promotes the formation of hnRNPK phase-separated condensates.
Fig. 7: MIRE accelerates tumor cell growth via hnRNPK.

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Data availability

The RNA sequencing data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus with accession code GSE218179.

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Acknowledgements

This work was supported by grants from the Ministry of Science and Technology of China (2019YFA0802600), the National Natural Science Foundation of China (91957108, 31871440, and 32270811), and the Fundamental Research Funds For Central Universities (YD9100002012 and WK9100000024).

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  1. The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China

    Bingyan Li, Bo Yao, Xiaorui Guo, Zhongyu Wang, Xianning Wu, Fang Wang & Yide Mei

  2. The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China

    Wei Xie & Yide Mei

  3. DeepBio Technology Ltd Co., 515 ShenNan Road, Shanghai, 201612, China

    Wei Xie

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BL, XW, FW, and YM designed research. BL, BY, XG, and ZW performed research. BL, BY, XG, ZW, WX, XW, FW, and YM analyzed data. BL, FW, and YM wrote the paper.

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Correspondence to Xianning Wu, Fang Wang or Yide Mei.

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Li, B., Yao, B., Guo, X. et al. c-Myc-induced long noncoding RNA MIRE cooperates with hnRNPK to stabilize ELF2 mRNA and promotes clear cell renal cell carcinogenesis. Cancer Gene Ther 30, 1215–1226 (2023). https://doi.org/10.1038/s41417-023-00631-0

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