Phenotypic miRNA Screen Identifies miR-26b to Promote the Growth and Survival of Endothelial Cells

• Main Authors: Andrea Martello (Author), David Mellis (Author), Marco Meloni (Author), Alison Howarth (Author), Daniel Ebner (Author), Andrea Caporali (Author), Ayman Al Haj Zen (Author)
• Format: Book
• Published: Elsevier, 2018-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Endothelial cell (EC) proliferation is a crucial event in physiological and pathological angiogenesis. MicroRNAs (miRNAs) have emerged as important modulators of the angiogenic switch. Here we conducted high-content screening of a human miRNA mimic library to identify novel regulators of EC growth systematically. Several miRNAs were nominated that enhanced or inhibited EC growth. Of these, we focused on miR-26b, which is a conserved candidate and expressed in multiple human EC types. miR-26b overexpression enhanced EC proliferation, migration, and tube formation, while inhibition of miR-26b suppressed the proliferative and angiogenic capacity of ECs. A combinatory functional small interfering RNA (siRNA) screening of 48 predicted gene targets revealed that miR-26b enhanced EC growth and survival through inhibiting PTEN expression. Local administration of miR-26b mimics promoted the growth of new microvessels in the Matrigel plug model. In the mouse model of hindlimb ischemia, miR-26b was found to be downregulated in endothelium in the first week following ischemia, and local overexpression of miR-26b improved the survival of capillaries and muscle fibers in ischemic muscles. Our findings suggest that miR-26b enhances EC proliferation, survival, and angiogenesis. miR-26b is a potential target for developing novel pro-angiogenic therapeutics in ischemic disease. Keywords: high content screen, miRNA mimic library, miR-26b, endothelial cells, cell growth

Item Description

2162-2531
10.1016/j.omtn.2018.08.006