Loss of <i><scp>miR</scp>‐101</i> expression promotes Wnt/<i>β</i>‐catenin signalling pathway activation and malignancy in colon cancer cells

<jats:title>Abstract</jats:title><jats:p><jats:bold>Colorectal cancer (<jats:styled-content style="fixed-case">CRC</jats:styled-content>) is the second leading cause of cancer‐related mortality in Western countries. Although the aberrant expression of several <jats:styled-content style="fixed-case">microRNAs</jats:styled-content> (<jats:styled-content style="fixed-case">oncomiRs</jats:styled-content>) is associated with <jats:styled-content style="fixed-case">CRC</jats:styled-content> progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that <jats:italic><jats:styled-content style="fixed-case">miR</jats:styled-content>‐101</jats:italic> expression is differentially impaired in <jats:styled-content style="fixed-case">CRC</jats:styled-content> specimens, depending on tumour grade. <jats:italic><jats:styled-content style="fixed-case">miR</jats:styled-content>‐101</jats:italic> re‐expression suppresses cell growth in <jats:styled-content style="fixed-case">3D</jats:styled-content>, hypoxic survival and invasive potential in <jats:styled-content style="fixed-case">CRC</jats:styled-content> cells showing low levels of <jats:italic><jats:styled-content style="fixed-case">miR</jats:styled-content>‐101</jats:italic>. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between <jats:italic><jats:styled-content style="fixed-case">miR</jats:styled-content>‐101</jats:italic> expression and important <jats:styled-content style="fixed-case">CRC</jats:styled-content> pro‐malignant features, such as inflammation, activation of the Wnt/<jats:italic>β</jats:italic>‐catenin signalling pathway and epithelial–mesenchymal transition (<jats:styled-content style="fixed-case">EMT</jats:styled-content>). We then propose that up‐regulated <jats:italic><jats:styled-content style="fixed-case">miR</jats:styled-content>‐101</jats:italic> may function as a tumour suppressor in <jats:styled-content style="fixed-case">CRC</jats:styled-content> and that its pharmacological restoration might hamper the aggressive behaviour of <jats:styled-content style="fixed-case">CRC</jats:styled-content> <jats:italic>in vivo</jats:italic>. <jats:italic><jats:styled-content style="fixed-case">MiR</jats:styled-content>‐101</jats:italic> expression may also represent a cancer biomarker for <jats:styled-content style="fixed-case">CRC</jats:styled-content> diagnosis and prognosis. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</jats:bold></jats:p>