MiR-590-5p, a density-sensitive microRNA, inhibits tumorigenesis by targeting YAP1 in colorectal cancer

Abstract

YAP1, a transcription co-activator, mediates the biological functions of the Hippo pathway. YAP1 inactivation is involved in cell-cell contact inhibition. In various tumors, YAP1 is upregulated through multiple mechanisms, and it functions as an oncogene. Here, we provided evidence that YAP1 influenced multiple signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and in vivo xenograft model. We analyzed different cell densities and found that increased density caused increased expression of miR-590-5p, and decreased expression of its precursors (pri- and pre-miR-590). Increasing cancer cell density upregulated the expression of a RNase III endonuclease, DICER1. DICER1 increased miR-590 biogenesis and inhibited YAP1. In DICER1-defective CRC cells, addition of pre-miR-590 did not inhibit YAP1 expression. Analyses of clinical data demonstrated that the DICER1-miR-590-5p-YAP1 axis was dysregulated in CRC specimens and affected patient survival. Cell-cell contact inhibition is crucial to prevent uncontrolled cell proliferation. Identification of this cell density-sensitive, DICER1-miR-590-5p-YAP1 axis may provide a basis for developing new biomarkers or targeted therapies for CRC.

Keywords: Cell density; Colorectal cancer; Hippo pathway; YAP1; miR-590-5p.