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Supplementary Figure Legends from miR-508 Defines the Stem-like/Mesenchymal Subtype in Colorectal Cancer

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journal contribution
posted on 2023-03-31, 01:22 authored by Ting-Ting Yan, Lin-Lin Ren, Chao-Qin Shen, Zhen-Hua Wang, Ya-Nan Yu, Qian Liang, Jia-Yin Tang, Ying-Xuan Chen, Dan-Feng Sun, Witold Zgodzinski, Marek Majewski, Piotr Radwan, Ilona Kryczek, Ming Zhong, Jinxian Chen, Qiang Liu, Weiping Zou, Hao-Yan Chen, Jie Hong, Jing-Yuan Fang

This file contains figure legends corresponding to supplementary figures.

Funding

National Natural Science Foundation of China

Shanghai Natural Science Foundation

Shanghai Municipal Education Commission

History

ARTICLE ABSTRACT

Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its genetic drivers, functional, and clinical relevance are uncharacterized. Here we report the definition of an altered miRNA signature defining this subtype that includes a major genomic loss of miR-508. Mechanistic investigations showed that this miRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic expression of miR-508 in colorectal cancer cells blunted epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo. In clinical colorectal cancer specimens, expression of miR-508 negatively correlated with stemness and EMT-associated gene expression and positively correlated with patient survival. Overall, our results showed that miR-508 is a key functional determinant of the stem-like/mesenchymal colorectal cancer subtype and a candidate therapeutic target for its treatment.Significance: These results define a key functional determinant of a stem-like/mesenchymal subtype of colorectal cancers and a candidate therapeutic target for its treatment. Cancer Res; 78(7); 1751–65. ©2018 AACR.