In vivo studies of an axis driving cancer progression

The Zeb1/miR200 axis has been implicated in the regulation of a crucial transition in cancer. However, in vivo studies of the relevance of this axis have been lacking. The lab of NCCR RNA & Disease principal investigator Markus Stoffel now reports their in vivo findings regarding this axis in a Nature Communications article entitled "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.

Read the Publication in Nature Communications (Open Access)

Website Stoffel Lab

Abstract and figure image from Title et al. (2018) Nature Communications, 9(1),4671 published under the CC BY 4.0 license