No abstract

Although specific microRNAs (miRNAs) can be upregulated in cancer, global miRNA downregulation is a common trait of human malignancies. The mechanisms of this phenomenon and the advantages it affords remain poorly understood. Here we identify a microRNA family, miR-103/107, that attenuates miRNA biosynthesis by targeting Dicer, a key component of the miRNA processing machinery. In human breast cancer, high levels of miR-103/107 are associated with metastasis and poor outcome. Functionally, miR-103/107 confer migratory capacities in vitro and empower metastatic dissemination of otherwise nonaggressive cells in vivo. Inhibition of miR-103/107 opposes migration and metastasis of malignant cells. At the cellular level, a key event fostered by miR-103/107 is induction of epithelial-to-mesenchymal transition (EMT), attained by downregulating miR-200 levels. These findings suggest a new pathway by which Dicer inhibition drifts epithelial cancer toward a less-differentiated, mesenchymal fate to foster metastasis.

Hi-C is a genome-wide sequencing technique to investigate the 3D chromatin conformation inside the nucleus. The most studied structures that can be identified from Hi-C - chromatin interactions and topologically associating domains (TADs) - require computational methods to analyze genome-wide contact probability maps. We quantitatively compared the performances of 13 algorithms for the analysis of Hi-C data from 6 landmark studies and simulations. The comparison revealed clear differences in the performances of methods to identify chromatin interactions and more comparable results of algorithms for TAD detection.