Combinatorial Targeting by MicroRNAs Co-ordinates Post-transcriptional Control of EMT

Cell Systems
Joseph CursonsMelissa J Davis

Abstract

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, functioning in part by facilitating the degradation of target mRNAs. They have an established role in controlling epithelial-mesenchymal transition (EMT), a reversible phenotypic program underlying normal and pathological processes. Many studies demonstrate the role of individual miRNAs using overexpression at levels greatly exceeding physiological abundance. This can influence transcripts with relatively poor targeting and may in part explain why over 130 different miRNAs are directly implicated as EMT regulators. Analyzing a human mammary cell model of EMT we found evidence that a set of miRNAs, including the miR-200 and miR-182/183 family members, co-operate in post-transcriptional regulation, both reinforcing and buffering transcriptional output. Investigating this, we demonstrate that combinatorial treatment altered cellular phenotype with miRNA concentrations much closer to endogenous levels and with less off-target effects. This suggests that co-operative targeting by miRNAs is important for their physiological function and future work classifying miRNAs should consider such combinatorial effects.

Citations

Dec 18, 2018·Physical Biology·Dongya JiaHerbert Levine
Apr 28, 2019·Genes·Sebastian Kittelmann, Alistair P McGregor
Nov 30, 2018·Scientific Reports·Giorgi MargvelaniRevaz Solomonia
Oct 28, 2019·Genome Research·Jennifer M CheroneChristopher B Burge
Jul 29, 2020·International Journal of Molecular Sciences·Boris SabirzhanovBogdan A Stoica
Nov 8, 2018·BMC Bioinformatics·Momeneh ForoutanMelissa J Davis
Dec 4, 2019·PLoS Computational Biology·Vu V H PhamThuc D Le
Apr 23, 2020·Frontiers in Oncology·Ilias Georgakopoulos-SoaresApostolos Zaravinos
Oct 1, 2020·Nucleic Acids Research·Dharmesh D BhuvaMelissa J Davis
Oct 22, 2020·Nature Reviews. Cancer·Gregory J Goodall, Vihandha O Wickramasinghe
May 16, 2019·Cancer Immunology Research·Joseph CursonsMelissa J Davis
Jan 1, 2021·Bioinformatics·Vu V H PhamThuc D Le
Apr 24, 2021·Nucleic Acid Therapeutics·Nahid Arghiani, Maryam M Matin
May 5, 2021·The Journal of Clinical Investigation·Isabella I SanchezLeslie M Thompson

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