1. Academic Validation
  2. RANBP1 promotes colorectal cancer progression by regulating pre-miRNA nuclear export via a positive feedback loop with YAP

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

  • Oncogene. 2022 Feb;41(7):930-942. doi: 10.1038/s41388-021-02036-5.
Dandan Zheng  # 1 Meng Cao  # 2 Siyu Zuo  # 1 3 Xin Xia 1 Chunchun Zhi 4 Yanbing Lin 1 Sitong Deng 1 Xiaoqin Yuan 5 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China.
  • 2 Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
  • 3 The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310003, China.
  • 4 Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.
  • 5 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China. [email protected].
  • 6 Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, 211166, China. [email protected].
  • # Contributed equally.
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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