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RANBP1 promotes colorectal cancer progression by regulating pre-miRNA nuclear export via a positive feedback loop with YAP

Oncogene volume 41, pages 930–942 (2022)Cite this article

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A Correction to this article was published on 04 January 2022

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Abstract

Colorectal cancer (CRC) is among the top five most common malignant tumors worldwide and has a high mortality rate. Identification of the mechanism of CRC and potential therapeutic targets is critical for improving survival. In the present study, we observed high expression of RAN binding protein 1 (RANBP1) in CRC tissues. Upregulated RANBP1 expression was strongly associated with TNM stages and was an independent risk factor for poor prognosis. In vitro and in vivo functional experiments demonstrated that RANBP1 promoted the proliferation and invasion of CRC cells and inhibited the apoptosis of CRC cells. Low RANBP1 expression reduced the expression levels of hsa-miR-18a, hsa-miR-183, and hsa-miR-106 microRNAs (miRNAs) by inhibiting the nucleoplasmic transport of precursor miRNAs (pre-miRNAs), thereby promoting the accumulation of the latter in the nucleus and reducing the expression of mature miRNAs. Further experiments and bioinformatic analyses demonstrated that RANBP1 promoted the expression of YAP by regulating miRNAs and the Hippo pathway. We also found that YAP acted as a transcriptional cofactor to activate RANBP1 transcription in combination with TEAD4 transcription factor. Thus, RANBP1 further promoted the progression of CRC by forming a positive feedback loop with YAP. Our results revealed the biological role and mechanism of RANBP1 in CRC for the first time, suggesting that RANBP1 can be used as a diagnostic molecule and a potential therapeutic target in CRC.

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Fig. 1: RANBP1 is upregulated in CRC tissues and is associated with poor prognosis in CRC patients.
Fig. 2: RANBP1 promotes cell proliferation and invasion in vitro.
Fig. 3: RANBP1 accelerates the proliferation and metastasis of CRC cells in vivo.
Fig. 4: RANBP1 affects miRNA expression in CRC cells.
Fig. 5: RANBP1 regulates precursor miRNA nuclear export.
Fig. 6: RANBP1 regulates the Hippo signaling pathway via miRNA.
Fig. 7: RANBP1 is transcriptionally activated by YAP–TEAD4.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (no. 81972288) and the General Project of the Natural Science Foundation of Jiangsu Province (no. BK20191353).

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Author notes

  1. These authors contributed equally: Dandan Zheng, Meng Cao, Siyu Zuo.

Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China

    Dandan Zheng, Siyu Zuo, Xin Xia, Yanbing Lin, Sitong Deng & Xiaoqin Yuan

  2. Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Meng Cao

  3. The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310003, China

    Siyu Zuo

  4. Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China

    Chunchun Zhi

  5. Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, 211166, China

    Xiaoqin Yuan

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Contributions

XY designed the study and wrote the manuscript. DZ and SZ developed the methodology and performed the analyses. MC and CZ collected and analyzed the clinical data. XX performed the statistical analysis. YL and SD performed the bioinformatics analysis. The authors read and approved the final manuscript.

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Correspondence to Xiaoqin Yuan.

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Zheng, D., Cao, M., Zuo, S. et al. RANBP1 promotes colorectal cancer progression by regulating pre-miRNA nuclear export via a positive feedback loop with YAP. Oncogene 41, 930–942 (2022). https://doi.org/10.1038/s41388-021-02036-5

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