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A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability

Author

Listed:
  • Ke Li

    (West China Hospital, Sichuan University)

  • Jiawei Guo

    (West China Hospital, Sichuan University)

  • Yue Ming

    (West China Hospital, Sichuan University)

  • Shuang Chen

    (West China Hospital, Sichuan University)

  • Tingting Zhang

    (West China Hospital, Sichuan University)

  • Hulin Ma

    (West China Hospital, Sichuan University)

  • Xin Fu

    (West China Hospital, Sichuan University)

  • Jin Wang

    (West China Hospital, Sichuan University)

  • Wenrong Liu

    (West China Hospital, Sichuan University)

  • Yong Peng

    (West China Hospital, Sichuan University
    Tianfu Jincheng Laboratory)

Abstract

Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy.

Suggested Citation

  • Ke Li & Jiawei Guo & Yue Ming & Shuang Chen & Tingting Zhang & Hulin Ma & Xin Fu & Jin Wang & Wenrong Liu & Yong Peng, 2023. "A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42571-1
    DOI: 10.1038/s41467-023-42571-1
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    1. Sebastian Memczak & Marvin Jens & Antigoni Elefsinioti & Francesca Torti & Janna Krueger & Agnieszka Rybak & Luisa Maier & Sebastian D. Mackowiak & Lea H. Gregersen & Mathias Munschauer & Alexander Lo, 2013. "Circular RNAs are a large class of animal RNAs with regulatory potency," Nature, Nature, vol. 495(7441), pages 333-338, March.
    2. Paula D. Bos & Xiang H.-F. Zhang & Cristina Nadal & Weiping Shu & Roger R. Gomis & Don X. Nguyen & Andy J. Minn & Marc J. van de Vijver & William L. Gerald & John A. Foekens & Joan Massagué, 2009. "Genes that mediate breast cancer metastasis to the brain," Nature, Nature, vol. 459(7249), pages 1005-1009, June.
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