MiR-signing gastrointestinal (con-)tract cancer

MicroRNAs (miRs) are evolutionary conserved, small non-coding RNAs with a crucial role in regulating genes expression [1]. As they target simultaneously several genes, one miR can eventually control a variety of cellular functions. Therefore, aberrations in the expression of miRs have detrimental repercussions for disease development and progression, including cancer. In the current issue, the Blandino group elegantly demonstrated that mir-204 is significantly downregulated in tumors of the gastrointestinal tract [2]. Mir-204 is deregulated in many types of cancer, exhibiting a tumorsuppressor role in the majority of them. Although evidence has implicated mir-204 in the development of gastric and esophageal cancer, a systematic in vivo analysis to define its targets and address the functional consequences from escaping mir-204 suppression was missing in tumors of the gastrointestinal tract [1]. Focusing in parallel into gastric cancer and cholangiocarcinoma, a rare tumor type of the digestive system, Canu and collaborators provide evidence that mir-204 downregulation is associated with a specifically altered 7-gene expression signature [2]. In silico and functional analyses demonstrated that all 7 genes (Figure 1) (CENP-A, SHCBP-1, FOXM1, KIF15, CENP-E, RAD51 and NOTCH1) in this signature were direct targets of mir-204, each influencing in an additive manner cell cycle progression and clonogenicity in corresponding cellular systems. At a first glance all seven genes seem to be almost unrelated, yet a closer examination reveals a potential synergy between them, providing a functional frame for these findings. The most central, orchestrating, gene seems to be FOXM1. It is a transcription factor that stimulates S and M phase entry and is overexpressed in News