KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling
Feng Du, Tianyu Cao, Huahong Xie, Ting Li, Lina Sun, Hao Liu, Hao Guo, Xin Wang, Qi Liu, Tae‐Wan Kim, Jeffrey L. Franklin, Ramona Graves‐Deal, Weili Han, Zuhong Tian, Minghui Ge, Yongzhan Nie, Daiming Fan, Robert J. Coffey, Yuanyuan Lu, Xiaodi Zhao
Abstract
We identified miR-139-5p as a KRAS-responsive miRNA and demonstrated its involvement in CRC progression. KRAS mutation disrupted the miR-139-5p/Wnt signaling reciprocal negative feedback mechanism, which might cause miR-139-5p downregulation and derepression of oncogenic signaling pathways and EMT. These results reveal a transcriptional regulatory mode of KRAS-driven malignant transformation and highlight miR-139-5p as a novel regulator of crosstalk between the Ras and Wnt signaling pathways in CRC.