In this study, we disclose a novel AP-1/miR-101 regulatory circuitry, that is, AP-1 promotes the transcription of miR-101, whereas the expression of miR-101 reduces the levels of ERK2 and c-Fos and thereby attenuates the AP-1 signaling and in turn abrogates the AP-1-promoted migration and invasion of cancer cells. This evidence concerns the gene JUN and cancer.