| Title |
High-content analysis of microRNAs involved in the phenotype regulation of vascular smooth muscle cells / |
| Authors |
Zhang, Jian ; Starkuvienė-Erfle, Vytautė ; Erfle, Holger ; Wang, Zhaohui ; Gunkel, Manuel ; Zeng, Ziwei ; Sticht, Carsten ; Kan, Kejia ; Rahbari, Nuh ; Keese, Michael |
| DOI |
10.1038/s41598-022-07280-7 |
| Full Text |
|
| Is Part of |
Scientific reports.. Berlin : Nature Portfolio. 2022, vol. 12, iss. 1, art. no. 3498, p. [1-13].. ISSN 2045-2322 |
| Keywords [eng] |
switch phenotype ; miRNAs ; VSMC |
| Abstract [eng] |
In response to vascular injury vascular smooth muscle cells (VSMCs) alternate between a differentiated(contractile) and a dedifferentiated (synthetic) state or phenotype. Although parts of the signalingcascade regulating the phenotypic switch have been described, the role of miRNAs is still incompletelyunderstood. To systematically address this issue, we have established a microscopy‑basedquantitative assay and identified 23 miRNAs that induced contractile phenotypes when over‑expressed. These were then correlated to miRNAs identified from RNA‑sequencing when comparingcells in the contractile and synthetic states. Using both approaches, six miRNAs (miR‑132‑3p, miR‑138‑5p, miR‑141‑3p, miR‑145‑5p, miR‑150‑5p, and miR‑22‑3p) were filtered as candidates that inducethe phenotypic switch from synthetic to contractile. To identify potentially common regulatorymechanisms of these six miRNAs, their predicted targets were compared with five miRNAs sharingZBTB20, ZNF704, and EIF4EBP2 as common potential targets and four miRNAs sharing 16 commonpotential targets. The interaction network consisting of these 19 targets and additional 18 hub targetswere created to facilitate validation of miRNA‑mRNA interactions by suggesting the most plausiblepairs. Furthermore, the information on drug candidates was integrated into the network to predictnovel combinatorial therapies that encompass the complexity of miRNAs‑mediated regulation.This is the first study that combines a phenotypic screening approach with RNA sequencing andbioinformatics to systematically identify miRNA‑mediated pathway (2) (PDF) High-content analysis of microRNAs involved in the phenotype regulation of vascular smooth muscle cells. Available from: https://www.researchgate.net/publication/358990313_High-content_analysis_of_microRNAs_involved_in_the_phenotype_regulation_of_vascular_smooth_muscle_cells [accessed Nov 09 2022]. |
| Published |
Berlin : Nature Portfolio |
| Type |
Journal article |
| Language |
English |
| Publication date |
2022 |
| CC license |
|
