TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000293549
  • Gene Name:WNT1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

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

Disease basic infommation

  • Disease:breast cancer
  • Tissue:HEK 293T (human embryonic kidney 293T) and human breast cancercell lines ZR-75-30 (human breast ductal carcinoma), MDA-MB-231 (human breast adenocarcinoma), MCF7 (human breast adenocarcinoma) and T-47D (human breast ductal carcinoma)

Other information

  • Title:The Wnt-β-catenin pathway represses let-7 microRNA expression through transactivation of Lin28 to augment breast cancerstem cell expansion.
  • Journal:J Cell Sci
  • Published:2013
  • PubMed ID:23613467
  • Abstract:Wnt signalling through β-catenin and the lymphoid-enhancing factor 1/T-cell factor (LEF1/TCF) family of transcription factors maintains stem cell properties in both normal and malignant tissues; however, the underlying molecular pathway involved in this process has not been completely defined. Using a microRNA microarray screening assay, we identified let-7 miRNAs as downstream targets of the Wnt-β-catenin pathway. Expression studies indicated that the Wnt-β-catenin pathway suppresses mature let-7 miRNAs but not the primary transcripts, which suggests a post-transcriptional regulation of repression. Furthermore, we identified Lin28, a negative let-7 biogenesis regulator, as a novel direct downstream target of the Wnt-β-catenin pathway. Loss of function of Lin28 impairs Wnt-β-catenin-pathway-mediated let-7 inhibition and breast cancer stem cell expansion; enforced expression of let-7 blocks the Wnt-β-catenin pathway-stimulated breast cancer stem cell phenotype. Finally, we demonstrated that the Wnt-β-catenin pathway induces Lin28 upregulation and let-7 downregulation in both cancer samples and mouse tumour models. Moreover, the delivery of a modified lin28 siRNA or a let-7a agomir into the premalignant mammary tissues of MMTV-wnt-1 mice resulted in a complete rescue of the stem cell phenotype driven by the Wnt-β-catenin pathway. These findings highlight a pivotal role for Lin28/let-7 in Wnt-β-catenin-pathway-mediated cellular phenotypes. Thus, the Wnt-β-catenin pathway, Lin28 and let-7 miRNAs, three of the most crucial stem cell regulators, connect in one signal cascade.
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