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

Hsin Yi Chen, Yaw Dong Lang, Han Nan Lin, Yun Ru Liu, Chun Chieh Liao, André Wendindondé Nana, Yun Yen, Ruey Hwa Chen

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

Cancer stemness drives tumor initiation, progression, metastasis, recurrence, and therapy resistance. However, mechanisms that potentiate the acquisition and maintenance of stemness 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 stem-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. Mechanistically, these stemness-promoting functions are mediated by miR-103/107-dependent repression of Axin2, a negative feedback regulator of Wnt/β-catenin signaling. Through inhibiting Axin2, miR-103/107 trigger a prolonged duration of Wnt/β-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 stemness by targeting Axin2 and elucidates the clinical relevance and prognostic value of this axis in colorectal cancer.

原文英語
文章編號9687
期刊Scientific Reports
9
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2019

ASJC Scopus subject areas

  • General

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