Copy number variants (CNVs) are associated with changes in gene expression levels and contribute to various adaptive traits. Here we show that a CNV at the Grain Length on Chromosome 7 (GL7) locus contributes to grain size diversity in rice (Oryza sativa L.). GL7 encodes a protein homologous to Arabidopsis thaliana LONGIFOLIA proteins, which regulate longitudinal cell elongation. Tandem duplication of a 17.1-kb segment at the GL7 locus leads to upregulation of GL7 and downregulation of its nearby negative regulator, resulting in an increase in grain length and improvement of grain appearance quality. Sequence analysis indicates that allelic variants of GL7 and its negative regulator are associated with grain size diversity and that the CNV at the GL7 locus was selected for and used in breeding. Our work suggests that pyramiding beneficial alleles of GL7 and other yield- and quality-related genes may improve the breeding of elite rice varieties.

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.

MicroRNA-128 (miR-128) is reduced in prostate cancer (PCa) relative to normal/benign prostate tissues but causal roles are obscure. Here we show that exogenously introduced miR-128 suppresses tumor regeneration in multiple PCa xenograft models. Cancer stem-like cell (CSC) associated properties were blocked, including holoclone and sphere formation as well as clonogenic survival. Using a miR-128 sensor to distinguish cells on the basis of miR-128 expression, we found that miR-128-lo cells possessed higher clonal, clonogenic and tumorigenic activities than miR-128-hi cells. miR-128 targets the stem cell regulatory factors BMI-1, NANOG, and TGFBR1, the expression of which we found to vary inversely with miR-128 expression in PCa stem/progenitor cell populations. In particular, we defined BMI-1 as a direct and functionally relevant target of miR-128 in PCa cells, where these genes were reciprocally expressed and exhibited opposing biological functions. Our results define a tumor suppressor function for miR-128 in PCa by limiting CSC properties mediated by BMI-1 and other central stem cell regulators, with potential implications for PCa gene therapy.