title: miR-135a inhibition protects A549 cells from LPS-induced apoptosis by targeting Bcl-2.
abstract: Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality. Apoptosis is a key pathologic feature of ALI, and Bcl-2 plays an important role during the pathogenesis of ALI via the regulation of apoptosis. However, the regulation of Bcl-2 during ALI, particularly through microRNAs, remains unclear. We hypothesize that certain miRNAs may play deleterious or protective roles in ALI via the regulation of Bcl-2. The LPS stimulation of A549 cells was used to mimic ALI in vitro. First, we confirmed that Bcl-2 is involved in LPS-induced apoptosis in A549 cells. Then, bioinformatic analyses and quantitative real-time polymerase chain reaction assays were performed to screen for miRNAs targeting Bcl-2. We observed that miR-135a was markedly increased in LPS-challenged A549 cells. miR-135a inhibition markedly restored Bcl-2 expression and protected A549 cells from LPS-induced apoptosis. Furthermore, bioinformatic analysis and luciferase activity assays were conducted to confirm that miR-135a binds directly to the 3'-untranslated region of Bcl-2 and suppresses its expression. Interestingly, the inhibition of miR-135a did not attenuate apoptosis under LPS-treated conditions when Bcl-2 was knocked down. Therefore, we suggest that miR-135a regulation of LPS-induced apoptosis in A549 cells may depend in part on the regulation of Bcl-2. The miR-135a/Bcl-2 signaling pathway may be a novel therapeutic target for the prevention of ALI.
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zou
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Dianbin
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Radiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China. Electronic address: jianlinwu_du@163.com.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Wu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D035683:MicroRNAs / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Apoptosis; Bcl-2; Lipopolysaccharide; MicroRNA-135a