Priority Research Papers:
miR-151a enhances Slug dependent angiogenesis
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Douglas Jury1, Iben Daugaard1,2,3, Katie J. Sanders1, Lise Lotte Hansen2, Dritan Agalliu4,5 and Irene Munk Pedersen1,6
1 Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, USA
2 Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark
3 Department of Pathology, Aarhus University Hospital, Aarhus DK-8200, Denmark
4 Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA
5 Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA
6 Scintillon Institute, San Diego, CA 92121, USA
|Irene Munk Pedersen,||email:||[email protected]|
Keywords: angiogenesis; miR-151a; Slug; tumor microenvironment; endothelial cell
Received: August 10, 2019 Accepted: October 19, 2019 Published: June 09, 2020
MicroRNAs (miRs) are small non-coding RNAs, that modulate cognate gene expression either by inducing mRNA degradation or by blocking translation, and play crucial and complex roles in tissue homeostasis and during disease initiation and progression. The sprouting of new blood vessels by angiogenesis is critical in vascular development and homeostasis and aberrant angiogenesis is associated with pathological conditions such as ischemia and cancer. We have previously established that miR-151a functions as an onco-miR in non-small cell lung cancer (NSCLC) cells by inducing partial EMT and enhancing tumor growth. Here, we identify anti-miR-151a as a molecule that promotes endothelial cell contacts and barrier properties, suggesting that miR-151a regulates cell-cell junctions. We find that induced miR-151a expression enhances endothelial cell motility and angiogenesis and these functions depend on miR-151a-induced Slug levels. Moreover, we show that miR-151a overexpression enhances tumor-associated angiogenesis in 3D vascularized tumor spheroid assays. Finally, we verify that miR-151a is expressed in the vasculature of normal lung and NSCLC tissue. Our results suggest that miR-151a plays multi-faceted roles in the lung, by regulating multiple functions (cell growth, motility, partial EMT and angiogenesis) in distinct cell types.
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