miR-1199-5p and Zeb1 function in a double-negative feedback loop potentially coordinating EMT and tumour metastasis

Nature Communications
Maren DiepenbruckGerhard Christofori

Abstract

Epithelial tumour cells can gain invasive and metastatic capabilities by undergoing an epithelial-mesenchymal transition. Transcriptional regulators and post-transcriptional effectors like microRNAs orchestrate this process of high cellular plasticity and its malignant consequences. Here, using microRNA sequencing in a time-resolved manner and functional validation, we have identified microRNAs that are critical for the regulation of an epithelial-mesenchymal transition and of mesenchymal tumour cell migration. We report that miR-1199-5p is downregulated in its expression during an epithelial-mesenchymal transition, while its forced expression prevents an epithelial-mesenchymal transition, tumour cell migration and invasion in vitro, and lung metastasis in vivo. Mechanistically, miR-1199-5p acts in a reciprocal double-negative feedback loop with the epithelial-mesenchymal transition transcription factor Zeb1. This function resembles the activities of miR-200 family members, guardians of an epithelial cell phenotype. However, miR-1199-5p and miR-200 family members share only six target genes, indicating that, besides regulating Zeb1 expression, they exert distinct functions during an epithelial-mesenchymal transition.

References

Feb 13, 2003·Nucleic Acids Research·Rafael A IrizarryTerence P Speed
Feb 13, 2004·Bioinformatics·Laurent GautierRafael A Irizarry
Dec 28, 2006·BMC Medicine·Paolo P ProvenzanoPatricia J Keely
May 18, 2007·Nature Reviews. Cancer·Héctor PeinadoAmparo Cano
Apr 30, 2008·BMC Medicine·Paolo P ProvenzanoPatricia J Keely
Sep 6, 2008·The EMBO Journal·Francois LehembreGerhard Christofori
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Nov 26, 2009·Nature Cell Biology·Ulrich WellnerThomas Brabletz
Aug 14, 2010·EMBO Reports·Simone Brabletz, Thomas Brabletz
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Joseph H TaubeSendurai A Mani
Mar 26, 2011·Science·Christine L Chaffer, Robert A Weinberg
May 12, 2012·Nature Reviews. Cancer·Thomas Brabletz
Jun 4, 2013·Nature Cell Biology·Nora Pencheva, Sohail F Tavazoie
Nov 28, 2013·Molecular and Cellular Biology·Xiao Ling LiAshish Lal
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Apr 18, 2015·Journal of Oncology·Apostolos Zaravinos
Aug 1, 2015·Nature Methods·Harsh Dweep, Norbert Gretz
Jan 23, 2016·Nature·Joan Massagué, Anna C Obenauf
Feb 16, 2016·Nature Communications·Waltraut LehmannThomas Brabletz
Jul 2, 2016·Cell·M Angela NietoJean Paul Thiery
Oct 22, 2016·Current Opinion in Cell Biology·Maren Diepenbruck, Gerhard Christofori

❮ Previous
Next ❯

Citations

Jun 15, 2019·International Journal of Molecular Sciences·Yang HaoPeter Ten Dijke
Jan 11, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Guo-Biao XuPu Wang
Sep 22, 2018·Oncogenesis·Stefanie TiedeGerhard Christofori
Mar 1, 2019·Cancers·Shang-Gin WuJin-Yuan Shih
May 31, 2018·Non-coding RNA·Almudena Expósito-VillénDiego Franco
Sep 13, 2019·Molecular Cancer Research : MCR·Hyeon-Ju ChoKyung-Soon Park
Apr 4, 2020·Molecular Metabolism·Aarif Siddiqui, Paolo Ceppi
Oct 15, 2020·Journal of the Royal Society, Interface·Daner A SilveiraJosé Carlos M Mombach
Jan 29, 2021·Chemico-biological Interactions·Yan-Ni WangHua Miao
Feb 5, 2019·Developmental Cell·Nathalie Meyer-SchallerGerhard Christofori
Dec 12, 2020·ACS Applied Materials & Interfaces·Wei ZhouChunru Wang

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE32474
25
GSE86026

Methods Mentioned

BETA
fluorescence microscopy
FCS
transfection
immunoprecipitation
PCR
gene knockdown
ChIP
RNA assay
RNA-seq

Software Mentioned

MirWalk2
affy
miRWalk
Bioconductor package QuasR
GraphPad Prism
edgeR
Bioconductor
DAVID ( Database for Annotation , Visualization and Integrated...
STAR
Bowtie

Related Concepts