BackgroundIL‐37 has been identified as a fundamental inhibitor of inflammatory and immunity responses. It plays a crucial protective role in several cancers, but its anti‐tumor activity and the potential regulatory mechanism of IL‐37 in non‐small cell lung cancer (NSCLC) is largely unclear.MethodsEnzyme‐linked immunosorbent assay was used to detect plasma IL‐37 expression in NSCLC patients and healthy controls. The NSCLC cell line A549 was cultured with recombinant human IL‐37 or recombinant human IL‐6 protein. A549 invasion and metastasis were detected using Transwell invasion and scratch wound healing assays, respectively. Protein expression of STAT3, pSTAT3, E‐cadherin, vimentin, and N‐cadherin were detected using Western blotting, and messenger RNA expression of STAT3, E‐cadherin, vimentin, and N‐cadherin was assessed in each group using real time PCR.ResultsIL‐37 plasma expression was decreased in NSCLC patients, and the downregulation of IL‐37 was correlated with tumor stage. In vitro, IL‐37 inhibited invasion and migration in A549 cells, while IL‐6 promoted invasion and migration in A549 cells. pSTAT3, vimentin, and N‐cadherin expression was increased. E‐cadherin expression was lower in the IL‐6 group than in the control group; however, the opposite pattern was observed in the IL‐37 + IL‐6 group.ConclusionOur results showed that IL‐37 plays an inhibitory role in NSCLC progression, possibly by suppressing STAT3 activation and decreasing epithelial‐to‐mesenchymal transition by inhibiting IL‐6 expression. IL‐37 could serve as a potential novel tumor suppressor in NSCLC.
lation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress. Am J Physiol Cell Physiol 310: C755-C763, 2016. First published February 10, 2016 doi:10.1152/ajpcell.00226.2015.-Endoplasmic reticulum (ER) stress has been linked to the pathogenesis of Parkinson's disease (PD). However, the role of microRNAs (miRNAs) in this process involved in PD remains poorly understood. Recent studies indicate that miR-384-5p plays an important role for cell survival in response to different insults, but the role of miR-384-5p in PD-associated neurotoxicity remains unknown. In this study, we investigated the role of miR-384-5p in an in vitro model of PD using dopaminergic SH-SY5Y cells treated with rotenone. We found that miR-384-5p was persistently induced by rotenone in neurons. Also, the inhibition of miR-384-5p significantly suppressed rotenone-induced neurotoxicity, while overexpression of miR-384-5p aggravated rotenone-induced neurotoxicity. Through bioinformatics and dual-luciferase reporter assay, miR-384-5p was found to directly target the 3=-untranslated region of glucose-regulated protein 78 (GRP78), the master regulator of ER stress sensors. Quantitative polymerase chain reaction and Western blotting analysis showed that miR-384-5p negatively regulated the expression of GRP78. Inhibition of miR-384-5p remarkably suppressed rotenone-evoked ER stress, which was evident by a reduction in the phosphorylation of activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1␣). The downstream target genes of ER stress including CCAAT/enhancer-binding protein-homologous protein (CHOP) and X box-binding protein-1 (XBP-1) were also decreased by the miR-384-5p inhibitor. In contrast, overexpression of miR-384-5p enhanced ER stress signaling. In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitors on cell apoptosis and ER stress signaling. Moreover, we observed a significant increase of miR-384-5p expression in primary neurons induced by rotenone. Taken together, our results suggest that miR-384-5p mediated ER stress by negatively regulating GRP78 and that miR-384-5p inhibition might be a novel and promising approach for the treatment of PD. endoplasmic reticulum stress; Parkinson's disease; miR-384-
The present study aimed to observe the structural changes of the extracorticospinal tract in Parkinson's disease (PD) using susceptibility-weighted imaging (SWI) and diffusion tensor imaging (DTI) magnetic resonance (MR) scans. The association of DTI parameters and brain-iron accumulation with PD was examined and imaging signs useful in the diagnosis of PD were explored. The study included 30 patients with PD and 30 age- and gender-matched healthy controls who underwent routine MR, SWI and DTI scans. The corrected phase (CP) values of the substantia nigra (SN), red nucleus (RN), globus pallidus (GP) and putamen (PUT) were measured, and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained. Significant differences were found in the CP values between the PD and control groups in the SN, RN and PUT, but there were no differences in other regions of interest (ROIs). The FA values of the SN and PUT in the PD group were significantly decreased compared with those of the control group, but there was no significant difference in the FA values of the GP. Furthermore, there was no significant inter-group difference in the ADC values of any ROIs. In conclusion, SWI is a method useful for evaluating brain-iron deposition in PD. Increasing iron storage levels have previously been shown to be associated with PD pathogenesis but not with the degree of PD severity. FA values may be useful for diagnosing PD, and DTI may offer some insight into PD pathomechanisms and clinical diagnosis.
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