BackgroundKIT proto‐oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear.MethodsA total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA‐THYM) dataset were used to analyze KITLG related genome‐wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset‐GSE29695, including 37 samples was used as verification. For cell‐based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517.ResultsBoth datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA‐THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negative miRNAs, 28 hypermethylation and 163 hypomethylation regions. In the thymoma cell line Thy0517, it was found that the expression of GRB2 and the phosphorylation levels of BRAF, MEK1/2, and ERK1/2 in the MAPK pathway were positively correlated with the change in KITLG.ConclusionsHigh expression of KITLG is a new hallmark of WHO type A and AB thymomas in which it might play a critical role through the activation of the MAPK signaling pathway. Additionally, it is hoped that KITLG will become a potential target for the diagnosis of type A and AB thymoma through further research in the future.Key pointsSignificant findings of the studyKIT proto‐oncogene ligand (KITLG) is a new hallmark of type A and AB thymomas which induce a series of aberrant alteration of mRNA, miRNA and DNA methylation. The expression of KITLG is significantly higher in type A and AB than other subtypes of thymoma.What this study addsKITLG activated the MAPK signaling pathway to promote type A and AB thymoma which might be a potential diagnostic biomarker or target.
Objective Acute lung injury (ALI) caused by sepsis is clinically a syndrome, which is featured by damage to the alveolar epithelium and endothelium. In this study, we employed mice models of cecal ligation and puncture (CLP) and primary mice pulmonary microvascular endothelial cells (MPVECs) in vitro to investigate the effect of miR-128-3p in ALI caused by sepsis. Methods miR-128-3p agomir or randomized control were injected into adult male C57BL/6 mice 1 week before the CLP surgery. We used miR-128-3p agomir or scrambled control to transfect MPVECs and then employed lipopolysaccharide (LPS) stimulation on the cells. Pellino homolog 2 (PELI2) was predicted to be a direct target of miR-128-3p via luciferase reporter assay. MPVECs were cotransfected with lentiviral vector that expressed PELI2 (or empty vector) as well as miR-128-3p-mimics 1 day before LPS stimulation in rescue experiment. Transcriptional activity of caspase-3, cell apoptosis rate, and the expression levels of miR-128-3p, interleukin-1β (IL-1β), interleukin-6 (IL-6), and PELI2 were analyzed. Results Compared with the sham group, the lung of mice in the CLP group showed pulmonary morphological abnormalities, and the expression of IL-6 and IL-1β, caspase-3 activity, and apoptosis rate were significantly upregulated in the CLP group. Inflammatory factor levels and apoptosis rate were also significantly induced by LPS stimulation on MPVECs. Upregulation of miR-128-3p effectively inhibited sepsis-induced ALI, apoptosis as well as inflammation. miR-128-3p also played a role in antiapoptosis and anti-inflammation in MPVECs with LPS treatment. PEL12 upregulation in MPVECs alleviated miR-128-3p-induced caspase-3 activity inhibition and pro-inflammatory factor production. Conclusions miR-128-3p enabled to alleviate sepsis-induced ALI by inhibiting PEL12 expression, indicating a novel treatment strategy of miR-128-3p for sepsis-induced ALI.
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