The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter

Gollavilli PN, Parma B, Siddiqui A, Yang H, Ramesh V, Napoli F, Schwab A, Natesan R, Mielenz D, Asangani IA, Brabletz T, Pilarsky C, Ceppi P (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Oncogene Springer Nature

DOI: 10.1038/s41388-021-01708-6

Abstract

Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs endogenous levels and activity for in vitro and in vivo applications could lead to a better understanding of their biological role in physiology and disease.

Authors with CRIS profile

Paradesi Naidu Gollavilli Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 1 Prof. Dr. Ceppi Beatrice Parma Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 1 Prof. Dr. Ceppi Mohammad Siddiqui Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 1 Prof. Dr. Ceppi Hai Yang Department of Surgery Annemarie Schwab Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 1 Prof. Dr. Ceppi Dirk Mielenz Medizinische Fakultät Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Christian Pilarsky Professur für Chirurgische Forschung Paolo Ceppi Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 1 Prof. Dr. Ceppi

Involved external institutions

University of Pennsylvania US United States (USA) (US) University of Turin / Università degli Studi di Torino (UNITO) IT Italy (IT)

How to cite

APA:

Gollavilli, P.N., Parma, B., Siddiqui, A., Yang, H., Ramesh, V., Napoli, F.,... Ceppi, P. (2021). The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter. Oncogene. https://doi.org/10.1038/s41388-021-01708-6

MLA:

Gollavilli, Paradesi Naidu, et al. "The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter." Oncogene (2021).

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