Gene expression profiles of LS180 cells in which MYU, CTNNB1, or MYC expression was suppressed.

Aberrant activation of Wnt beta-catenin signalling is a major driving force in colon cancer. Wnt beta-catenin signalling induces the expression of the transcription factor c-Myc, leading to cell proliferation and tumourigenesis. c-Myc regulates multiple biological processes through its ability to directly modulate gene expression. However, the mechanisms underlying c-Myc-induced oncogenesis remain to be established. Here we identify a novel direct target of c-Myc, MYU (c-Myc-upregulated long non-coding RNA) and show that MYU is upregulated in most colon cancers and is required for the tumourigenicity of colon cancer cells. We further demonstrate that MYU associates with the RNA-binding protein hnRNP-K to stabilize CDK6 expression, and thereby promotes the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signalling and plays a critical role in the proliferation and tumourigenicity of colon cancer cells. MYU might be a promising molecular target for the therapeutic treatment of c-Myc-driven cancers.

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