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

Title, Alexandra C; Hong, Sue-Jean; Pires, Nuno D; Hasenöhrl, Lynn; Godbersen, Svenja; Stokar von Neuforn, Nadine; Bartel, David P; Stoffel, Markus (2018). Genetic dissection of the miR-200-Zeb1 axis reveals its importance in tumor differentiation and invasion. Nature communications, 9(1), p. 4671. Nature Publishing Group 10.1038/s41467-018-07130-z

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Stokar von Neuforn, Nadine

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

04 Jun 2019 15:49

Last Modified:

23 Oct 2019 03:42

Publisher DOI:

10.1038/s41467-018-07130-z

PubMed ID:

30405106

BORIS DOI:

10.7892/boris.127537

URI:

https://boris.unibe.ch/id/eprint/127537

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