MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes

• Published in: Nature communications Vol. 8; no. 1; pp. 14270 - 14
• Main Authors: Liu, Can, Liu, Ruifang, Zhang, Dingxiao, Deng, Qu, Liu, Bigang, Chao, Hsueh-Ping, Rycaj, Kiera, Takata, Yoko, Lin, Kevin, Lu, Yue, Zhong, Yi, Krolewski, John, Shen, Jianjun, Tang, Dean G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-01-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/100; 13/106; 13/31; 13/44; 13/89; 631/532/71; 631/67/589/466; Animals; Cell Line, Tumor; Cell Movement - physiology; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenetics; Gene Expression Regulation, Neoplastic - physiology; Genomes; Humanities and Social Sciences; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Male; Metastasis; Mice; Mice, SCID; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; multidisciplinary; Neoplasm Invasiveness; Neoplasms, Experimental; Neoplastic Stem Cells - metabolism; Prostate cancer; Prostatic Neoplasms - metabolism; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; Science; Science (multidisciplinary); Stem cells; Tumors; New York; United States > US; Texas
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14270

MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44
+
and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype. Whole-genome RNA sequencing uncovers novel miR-141-regulated molecular targets in PCa cells including the Rho GTPase family members (for example, CDC42, CDC42EP3, RAC1 and ARPC5) and stem cell molecules CD44 and EZH2, all of which are validated as direct and functionally relevant targets of miR-141. Our results suggest that miR-141 employs multiple mechanisms to obstruct tumour growth and metastasis.
MicroRNAs have important roles in regulating tumor development, progression and metastasis. Here, the authors demonstrate the tumor-suppressive functions of miRNA141 in prostate cancer stem cells mediated by directly targeting CD44, Rho GTPase protein family members, and EZH2.