Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (9): 74-84.doi: 10.6040/j.issn.1671-7554.0.2022.0429

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IGF2BP2/m6A/ITGA5 signal axis regulates the proliferation and migration of renal clear cells

ZHANG Zhenwei1, LI Jia2, CHEN Keming1   

  1. 1. Department of Urology, Jinan Third Peoples Hospital, Jinan 250132, Shandong, China;
    2. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
  • Published:2022-09-02

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Abstract: Objective To explore the potential role of m6A “recognition protein” insulin-like growth factor 2 mRNA binding protein(IGF2BP2)in clear cell renal cell carcinoma(ccRCC). Methods The expression of IGF2BP2 in ccRCC was searched in cancer gene database TCGA and analyzed with qRT-PCR and Western blotting. The m6A modification of ITGA5 mRNA was identified with methylated RNA immunoprecipitation qPCR combined with bioinformatics. IGF2BP2 on the regulation of ITGA5 expression was detected with gene knockdown/overexpression experiments, qRT-PCR and Western blotting. The biological roles of IGF2BP2 and ITGA5 in ccRCC cells were determined with gain- and loss-of-function experiments. Results Data from TCGA showed that IGF2BP2 was highly expressed in ccRCC, while the high expression was not conducive to the overall survival(HR=1.6, P=0.005)and disease-free survival(HR=1.9, P=0.014). Western blotting and qRT-PCR also indicated that IGF2BP2 was highly expressed. Western blotting revealed that IGF2BP2 expression was significantly higher in ccRCC cell lines than in normal renal epithelial cells. Gene set enrichment analysis(GSEA)showed that ITGA5 might be a downstream target of IGF2BP2. Further knockdown or overexpression suggested that IGF2BP2 regulated ITGA5 at the post-transcriptional level. Methylated RNA immunoprecipitation qPCR showed that m6A modification sites were in the 3'UTR region of ITGA5, and low m6A modifications helped to maintain the stability of mRNA. Conclusion IGF2BP2 is upregulated in ccRCC, which is unfavorable for the prognosis and survival. IGF2BP2/m6A/ITGA5 signal axis regulates the proliferation, migration and angiogenesis in ccRCC.

Key words: Clear cell renal cell carcinoma, Insulin-like growth factor 2 mRNA binding protein, N6-methyladenosine, Proliferation, Migration, Angiogenesis

CLC Number: 

  • R737.1
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