Genetic dissection of the miR-200–Zeb1 axis reveals its importance in tumor differentiation and invasion

The epithelial-to-mesenchymal transition (EMT) is an important mechanism for cancer progression and metastasis. Numerous in vitro and tumor-profiling studies point to the miR-200–Zeb1 axis as crucial in regulating this process, yet in vivo studies involving its regulation within a physiological context are lacking. Here, we show that miR-200 ablation in the Rip-Tag2 insulinoma mouse model induces beta-cell dedifferentiation, initiates an EMT expression program, and promotes tumor invasion. Strikingly, disrupting the miR-200 sites of the endogenous Zeb1 locus causes a similar phenotype. Reexpressing members of the miR-200 superfamily in vitro reveals that the miR-200c family and not the co-expressed and closely related miR-141 family is responsible for regulation of Zeb1 and EMT. Our results thus show that disrupting the in vivo regulation of Zeb1 by miR-200c is sufficient to drive EMT, thus highlighting the importance of this axis in tumor progression and invasion and its potential as a therapeutic target.National Institute of General Medical Sciences (U.S.

River histories : A thematic review

Peer reviewe

Bulbous gold–carbon nanodot hybrid nanoclusters for cancer therapy

Carbon nanodots are used to stabilize gold-nanoclusters. Charge-transfer interactions between carbon nanodots and gold were detected by transient absorption spectroscopy

Hamilton receptor-mediated self-assembly of orthogonally functionalized Au and TiO₂ nanoparticles

A new prototype of reversible self-assembly between functionalized gold and titanium dioxide nanoparticles (NPs) utilizing hydrogen bonding interactions was developed and established. The gold nanoparticles were functionalized with a Hamilton-receptor functionality bearing a thiol moiety as anchoring group. The titanium dioxide nanoparticles were modified with cyanurate derivatives which contained phosphonic acids as anchoring groups. The host–guest type interaction between two functionalized nanoparticles yielded a highly integrated nanoparticle system in chloroform. Moreover, by presenting a competing ligand in an exchange reaction, the product of self-assembly can be segregated into the individual soluble components of functionalized nanoparticles. The self-assembly and the exchange reaction were followed and monitored in detail by UV/Vis spectroscopy. The structure of the self-assembly product was investigated using scanning electron microscopy (SEM) and small-angle X-ray scattering (SAXS). © 2019 Wiley-VHCA AG, Zurich, Switzerlan