| Autor: |
Jing-Yuan Fang, Jie Hong, Hao-Yan Chen, Weiping Zou, Qiang Liu, Jinxian Chen, Ming Zhong, Ilona Kryczek, Piotr Radwan, Marek Majewski, Witold Zgodzinski, Dan-Feng Sun, Ying-Xuan Chen, Jia-Yin Tang, Qian Liang, Ya-Nan Yu, Zhen-Hua Wang, Chao-Qin Shen, Lin-Lin Ren, Ting-Ting Yan |
| Rok vydání: |
2023 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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