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Circular RNA EIF3I promotes papillary thyroid cancer progression by interacting with AUF1 to increase Cyclin D1 production

Oncogene volume 42, pages 3206–3218 (2023)Cite this article

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Abstract

Circular RNAs (circRNAs) play an important role in regulating the development of human cancers through diverse biological functions. However, the exact molecular mechanisms underlying the role of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. Here, we found that hsa_circ_0011385, designated as circular eukaryotic translation initiation factor 3 subunit I (circEIF3I), preferentially localized in the cytoplasm of PTC cells and was more stable than its linear counterpart, EIF3I. Gain- and loss-of-function studies indicated that circEIF3I promoted PTC progression by facilitating cell proliferation, cell cycle, cell migration, and invasion in vitro, as well as PTC cell proliferation in vivo. Mechanistically, circEIF3I interacted with AU-rich element (ARE) RNA-binding factor 1 (AUF1) in the cytoplasm of PTC cells, thus reducing the degradation of Cyclin D1 mRNA and increasing Cyclin D1 protein production, ultimately resulting in PTC progression. Collectively, our results demonstrate the vital role of circEIF3I in PTC progression, supporting its significance as a potential therapeutic target.

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Fig. 1: Identification and characterization of circEIF3I in PTC cells and tissues.
Fig. 2: Overexpression circEIF3I promotes PTC cells progression in vitro and in vivo.
Fig. 3: Knockdown of circEIF3I suppresses PTC cells progression in vitro.
Fig. 4: circEIF3I interacted with AUF1 in PTC cells.
Fig. 5: Overexpression circEIF3I promotes PTC cells progression in vitro.
Fig. 6: circEIF3I compromised AUF1 degradation of Cyclin D1 mRNA to promote PTC cell progression.
Fig. 7: AUF1 overexpression and Cyclin D1 knockdown rescued circEIF3I effects in promoting PTC progression.

Data availability

All data in our study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 32270590).

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Author notes

  1. These authors contributed equally: Xuelin Yao, Hanyuan Liu.

Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Xuelin Yao, Zhen Wang, Fangting Lu, Qing Feng, Yahu Miao, Jie Zhang, Yanlei Wang, Liping Xue & Qiu Zhang

  2. Department of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China

    Hanyuan Liu & Wenying Chen

  3. Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Ye Chen

  4. Department of Otorhinolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Yehai Liu

  5. Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, 230027, China

    Liang Chen

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Contributions

QZ, LC and YHL conceived, designed, and supervised all the experiments. XLY and HYL conducted the experiments and most of the analysis. ZW, QF, YHM, and FTL conducted the clinical data analysis. WYC performed circRNA circularization and RNA EMSA experiments. JZ, YLW, YC and LPX collected the tissue specimens. XLY and HYL wrote and revised the manuscript. LC provided critical discussions and the guidance suggestion to the revised manuscript. All authors read, discussed and approved the final version of the manuscript.

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Correspondence to Yehai Liu, Liang Chen or Qiu Zhang.

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Yao, X., Liu, H., Wang, Z. et al. Circular RNA EIF3I promotes papillary thyroid cancer progression by interacting with AUF1 to increase Cyclin D1 production. Oncogene 42, 3206–3218 (2023). https://doi.org/10.1038/s41388-023-02830-3

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