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

被引:0
|
作者
Dandan Zheng
Meng Cao
Siyu Zuo
Xin Xia
Chunchun Zhi
Yanbing Lin
Sitong Deng
Xiaoqin Yuan
机构
[1] Nanjing Medical University,Department of Anatomy, Histology and Embryology
[2] the Affiliated Hospital of Nanjing University Medical School,Department of General Surgery, Nanjing Drum Tower Hospital
[3] The Children’s Hospital,Department of Pathology, Nanjing Jinling Hospital
[4] Zhejiang University School of Medicine,Key Laboratory for Aging & Disease
[5] National Clinical Research Center for Child Health,undefined
[6] Nanjing University School of Medicine,undefined
[7] Nanjing Medical University,undefined
来源
Oncogene | 2022年 / 41卷
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摘要
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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页码:930 / 942
页数:12
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