Abstract
microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.
Highlights
MicroRNAs are approximately 22 nucleotides long non-coding RNA molecules that have been identified as important regulators in gene expression posttranscription
Cell viability decreased significantly when MLE-12 cells were treated with bleomycin at the concentrations of 50 and 100 mg/mL compared to the control group (Po0.05 or Po0.01; Figure 1A)
Cell viability was reduced, apoptotic cell number was increased and two pro-inflammatory factors (IL-1 and tumor necrosis factor-a (TNF-a)) were over-produced, which indicated MLE-12 cells were injured by bleomycin
Summary
MicroRNAs (miRNAs) are approximately 22 nucleotides long non-coding RNA molecules that have been identified as important regulators in gene expression posttranscription. Inflammation is triggered by infection or tissue injury involving coordinated recruitment of blood components (plasma and leukocytes) at the site of infection or injury [6,7]. These initial events are followed by production of various inflammatory mediators, which include prostaglandins, leukotrienes, prostacyclins, lymphokines, interferon-a (IFN-a), IFN-g, interleukin (IL)-1, IL-8, histamine, 5-hydroxytryptamine, tumor necrosis factor-a (TNF-a), vasoactive amines, eicosanoids and products of proteolytic cascades [8]. Treatment modalities available for IPF are ineffective at halting the disease progression It is a well-established fact that regulation of gene transcription in health and disease involves
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