TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000264235
  • Gene Name:GSK3B
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:Wnt/β-catenin
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:colorectal cancer
  • Tissue:Human CRC cell line SW480

Other information

  • Title:MiR-452 promotes an aggressive colorectal cancer phenotype by regulating a Wnt/β-catenin positive feedback loop
  • Journal:Journal of experimental & clinical cancer research : CR
  • Published:2018
  • PubMed ID:30253791
  • Abstract:Background:Aberrant activation of Wnt/β-catenin signaling pathway is considered to be an important issue in progression and metastasis of various human cancers, especially in colorectal cancer (CRC). MiR-452 could activate of Wnt/β-catenin signaling. But the mechanism remains unclear. Methods:The expression of miR-452 in CRC and normal tissues was detected by real-time quantitative PCR. The effect of miR-452 on CRC growth and invasion was conducted by functional experiments in vitro and in vivo. Bioinformatics and cell luciferase function studies verified the direct regulation of miR-452 on the 3＇-UTR of the GSK3β, which leads to the activation of Wnt/β-catenin signaling. Results:MiR-452 was upregulated in CRC compared with normal tissues and was correlated with clinical significance. The luciferase reporter system studies affirmed the direct regulation of miR-452 on the 3＇-UTR of the GSK3β, which activate the Wnt/β-catenin signaling. The ectopic upregulation of miR-452 significantly inhibited the expression of GSK3β and enhanced CRC proliferation and invasion in vitro and in vivo. Meanwhile, knockdown of miR-452 significantly recovered the expression of GSK3β and attenuated Wnt/β-catenin-mediated cell metastasis and proliferation. More important, T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors, which are crucial downstream molecules of the Wnt/β-catenin signaling pathway was verified as a valid transcription factor of miR-452＇s promoter. Conclusions:Our findings first demonstrate that miR-452-GSK3β-LEF1/TCF4 positive feedback loop induce CRC proliferation and migration.
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