Abstract:
: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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Liu C,Liu R,Zhang D,Deng Q,Liu B,Chao HP,Rycaj K,Takata Y,Lin K,Lu Y,Zhong Y,Krolewski J,Shen J,Tang DGdoi
10.1038/ncomms14270subject
Has Abstractpub_date
2017-01-23 00:00:00pages
14270issn
2041-1723pii
ncomms14270journal_volume
8pub_type
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