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EMX2OS targeting IGF2BP1 represses Wilms’ tumour stemness, epithelial–mesenchymal transition and metastasis

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Abstract

Wilms’ tumour (WT) is the most typical type of renal tumour in children, which has a poor prognosis and high recurrence rate. This study explored whether lncRNA EMX2 opposite strand / antisense RNA (EMX2OS) modulated the stemness, epithelial–mesenchymal transition (EMT) and metastasis of WT cells through the interaction with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The expression levels of EMX2OS, IGF2BP1 and stem cell markers OCT4, Nanog, Sox2 and CD133 were detected by real time quantitative polymerase chain reaction (RT-qPCR). The stemness, migration and invasion of WT cells were determined by sphere formation assay, scratch and transwell assay, respectively. The levels of EMT-related proteins were detected by Western blotting. RNA pull down and RIP assays were utilized to validate the interaction between EMX2OS and IGF2BP1. The tumourigenicity of WT cells in vivo was analysed using a xenograft tumour assay. EMX2OS was downregulated in WT patients, while IGF2BP1 was upregulated. EMX2OS overexpression or IGF2BP1 knockdown suppressed WT cell sphere formation, migration and invasion. Moreover, EMX2OS could directly interact with RNA-binding protein IGF2BP1, and IGF2BP1 overexpression counteracted the inhibitory effect of EMX2OS on WT cell stemness, migration, invasion and EMT. The in vivo tumour growth, stemness and EMT were repressed by EMX2OS through the interaction with IGF2BP1. In conclusion, EMX2OS acted as a tumour suppressor for WT by interacting with IGF2BP1, which might be a novel target for WT diagnosis and therapy.

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Authors and Affiliations

  1. Department of Urology, Qilu Children’s Hospital of Shandong University, Jinan, 250022, Shandong Province, People’s Republic of China

    Hong-Mei Zhang & Zhi-Hong Chen

  2. Department of Pediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong Province, People’s Republic of China

    Ming-Yu Cui

Authors
  1. Hong-Mei Zhang
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  2. Ming-Yu Cui
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Correspondence to Zhi-Hong Chen.

Additional information

Corresponding editor: Durgadas P. Kasbekar

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Zhang, HM., Cui, MY. & Chen, ZH. EMX2OS targeting IGF2BP1 represses Wilms’ tumour stemness, epithelial–mesenchymal transition and metastasis. J Genet 102, 12 (2023). https://doi.org/10.1007/s12041-022-01411-9

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  • DOI: https://doi.org/10.1007/s12041-022-01411-9

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