Emerging role of transcription factor-microRNA-target gene feed-forward loops in cancer

Transcriptional regulatory networks are biological network motifs that act in accordance with each other to play decisive roles in the pathological processes of cancer. One of the most common types, the feed-forward loop (FFL), has recently attracted interest. Three connected deregulated nodes, a transcription factor (TF), its downstream microRNA (miRNA) and their shared target gene can make up a class of cancer-involved FFLs as ≥1 of the 3 can act individually as a bona fide oncogene or a tumor suppressor. Numerous notable elements, such as p53, miR-17-92 cluster and cyclins, are proven members of their respective FFLs. Databases of interaction prediction, verification of experimental methods and confirmation of loops have been continually emerging during recent years. Development of TF-miRNA-target loops may help understand the mechanism of tumorgenesis at a higher level and explain the discovery and screening of the therapeutic target for drug exploitation.