Circular RNA VMA21 ameliorates lung injury in septic rat via targeting microRNA-497-5p/CD2-associated protein axis

Abstract

ABSTRACT Sepsis was characterized via an acute inflammatory response to infection, often accompanying by multiple organ failure, particularly lung damage. Circular RNA (circRNA) played an important role in the pathology of a variety of diseases. However, the role of circRNA in sepsis-induced lung injury (LI) remained unknown. This study was to explore the expression and role of circVMA21 in sepsis LI and the possible molecular mechanism. The results manifested circVMA21 and CD2-associated protein (CD2AP) were down-regulated in lung tissue and lipopolysaccharide (LPS)-treated BEAS-2B, while microRNA (miR)-497-5p was up-regulated. A large number of deaths in rats after surgery of 72 h were caused via cecal ligation-perforation surgery, W/D value and Bax positive cells were increased, LI was caused, cell apoptosis, tumor necrosis factor-α, Interleukin (IL)-1β and IL-6 expression were promoted and Bcl-2 positive cells were decreased. Overexpression of circVMA21 ameliorated these phenomena. In addition, LPS-induced apoptosis and inflammation of BEAS-2B cells was improved via overexpression of circVMA21, while overexpression of miR-497-5P was opposite. Apoptosis, inflammation, and oxidative damage of BEAS-2B cells were aggravated via knockdown of circVMA21, but it was reversed by knockdown of miR-497-5p or overexpression of CD2AP. Mechanistically, CircVMA21 mediated CD2AP expression through competitive adsorption of miR-497-5p. In conclusion, this work showed circVMA21 improved LI in sepsis rats by targeting miR-497-5p/CD2AP axis, suggesting that circVMA21 may be a novel therapeutic target for sepsis-induced LI.