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

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.

Sodium Butyrate Inhibits Colorectal Cancer Cell Migration by Downregulating Bmi‐1 Through Enhanced miR‐200c Expression

“…In LOVO cells, miR‐200a increased by 13‐fold and the other members of the miR‐200 family increased three‐ to eightfold after NaB treatment ( Figure A). Mir‐200 targets Bmi‐1, a component of the PRC1 polycomb complex, and EZH2, a component of the PRC2 polycomb complex . MiR‐200 also targets the ZEB1 transcriptional repressor, which is one of the master regulators in EMT .…”

“…Mir‐200 targets Bmi‐1, a component of the PRC1 polycomb complex, and EZH2, a component of the PRC2 polycomb complex . MiR‐200 also targets the ZEB1 transcriptional repressor, which is one of the master regulators in EMT . We evaluated the protein expression levels of these target genes.…”

miR‑202 suppresses prostate cancer growth and metastasis by targeting PIK3CA

“…Dysregulation of miRNA expression is often observed in human cancers, including PC (11). For example, miR-141 suppresses PC stem cells and metastasis by targeting a cohort of pro-metastasis genes (12). miR-194 suppresses PC cell migration and invasion by downregulating human nuclear distribution protein (13).…”

FilTar: Using RNA-Seq data to improve microRNA target prediction accuracy in animals

“…A summary of datasets used with relevant database accessions can be found in supplementary table 5 (Tamim et al 2014, Liu et al 2017, Stolzenburg et al 2016, Liu et al 2019, Guo et al 2014, Diepenbruck et al 2017, Pua et al 2016, Cao et al 2015.…”