microRNA suppresses prostate cancer stem cells and metastasis by inhibiting a cohort of pro-metastasis targets including CD44, Rho GTPases and EZH2

microRNA plays important roles in tumor initiation and progression. Here we showed that, one of the miR-200 family member, miR-141 is drastically under-expressed in several prostate cancer stem cell populations in both xenograft and primary patient samples. Enforced expression of miR-141 in CD44+ PCa cells suppressed tumor initation and metastasis. Cancer stem cell related properties including clonal and sphere formation ability as well as migration and invasion abilites were blocked by miR-141. Moreover, under-expression of miR-141 in prostate cancer stem cells is important in maintaining a partial mesenchymal status. Whole genome sequencing revealed novel pathways that are regulated by miR-141 including Rho GTPase signaling pathway. Stem cell related molecules including CD44 and EZH2 are also validated as direct targets of miR-141 mediating the tumor and metastasis suppressive function. Altogether, these data suggests that on e signal miRNA, miR-141 could utilize multiple mechanisms to obstruct tumor progression and metstasiss. Overall design: Total transcriptome profiles of prostate cancer cells Du145 and LAPC9 transfected with 30nM miR-141 mimicking oligonucleotides or negative control (NC) oligonucleotides were generated by deep sequencing, in duplicates, using Illumina HiSeq 2000.

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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 DG