Consistently, the depletion of miR143HG resulted in the opposite phenomenon of the aforementioned results. miR143HG inhibits miR-155 expression; miR-155 directly targets APC, which is a negative regulator of the Wnt/β-catenin pathway, so miR143HG can act on the Wnt pathway. miR143HG was further found to reduce the expression of β-catenin and block the nuclear accumulation of β-catenin, ultimately inhibiting the activation of the Wnt pathway.
Heterozygous <i>APC</i> gene mutations in FAP patients were associated with altered expression of candidate miRNAs and increased levels of <i>AXIN1</i> and <i>AXIN2</i> mRNAs. miR-155-5p was downregulated in FAP patients and in the <i>APC</i> and <i>β-CATENIN</i>-mutant colorectal cancer cell lines, and critically regulates WNT/β-CATENIN cascade by targeting both AXIN1 and TCF4.
Further studies revealed that APC is a novel miR-155 target, because miR-155 bound directly to its 3'-untranslated region and reduced both the mRNA and protein levels of APC.