miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2

Cancer sternness drives tumor initiation, progression, metastasis, recurrence, and therapy resistance. However, mechanisms that potentiate the acquisition and maintenance of sternness fate of cancer cells remain incompletely understood. Here, we show that miR-103/107 stimulate multiple stem-like features in colorectal cancer, including expression of stern-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. Mechanistically, these sternness-promoting functions are mediated by miR-103/107-dependent repression of Axin2, a negative feedback regulator ofWnt/beta-catenin signaling. Through inhibiting Axin2, miR-103/107 trigger a prolonged duration ofWnt/beta-catenin signaling and a sustained induction of Wnt responsive genes. In colorectal cancer patients, miR-103/107 expression correlates inversely with Axin2 expression and a signature of miR-103/107 high and Axin2 low expression profile correlates with poor prognosis. Together, our study identifies a novel function of miR-103/107 in promoting colorectal cancer sternness by targeting Axin2 and elucidates the clinical relevance and prognostic value of this axis in colorectal cancer.