Correlation between aluminum concentration and miR-134-3p expression in peripheral blood in occupational aluminum exposed workers / 环境与职业医学

Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q1-Q4) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P25, P75) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q1 group, blood aluminum in the Q2, Q3, or Q4 group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, Ptrend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (Ptrend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (Ptrend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Mechanisms for propofol in inhibiting the proliferation and invasion of glioma U87 cells and its effect on miR-134 expression / 中南大学学报(医学版)

OBJECTIVES@#To investigate the effects of propofol on the proliferation and invasion of glioma U87 cells and to explore the possible anti-tumor mechanisms.@*METHODS@#The glioma U87 cells was divided into a blank group, a positive control group, and the propofol groups (1.00, 2.00 or 5.00 mmol/L). Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell method was used to detect the effect of propofol on invasion and migration of U87 cells; real-time PCR was used to detect the expression of microRNA-134 (miR-134); Western blotting was used to detect the expression levels of reproduction-related protein Ki-67, invasion-related protein metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway-related protein.@*RESULTS@#Compared with the blank group, the proliferation, invasion and migration capacity of U87 cells were reduced in the positive control group and the propofol groups after 48 hours (all @*CONCLUSIONS@#Propofol can decrease the proliferation rate, and the invasion and migration abilities of U87 cells, which may be achieved by up-regulation of miR-134 and suppression of PI3K/Akt signaling pathway.

Long non-coding RNA FAM99A modulated YAP1 to affect trophoblast cell behaviors in preeclampsia by sponging miR-134-5p

Preeclampsia (PE) is a complex pregnancy syndrome. Convincing evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of PE. This research mainly investigated the mechanism of family with sequence similarity 99 member A (FAM99A) in PE. The expressions of FAM99A, miR-134-5p, and YAP1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis, migration, and invasion were detected by flow cytometry or transwell assay. The interaction between miR-134-5p and FAM99A or YAP1 was confirmed by dual-luciferase reporter assay. The protein expression of YAP1 was determined by western blot assay. FAM99A and YAP1 were significantly up-regulated, and miR-134-5p was significantly down-regulated in PE tissues (n=30). miR-134-5p was verified as a candidate of FAM99A and YAP1. FAM99A promoted cell metastasis, but reduced apoptosis in HTR8/SVneo cells by regulating miR-134-5p. miR-134-5p down-regulated YAP1 expression to suppress cell metastasis, while it induced apoptosis in HTR8/SVneo cells. FAM99A positively modulated YAP1 expression by sponging miR-134-5p. FAM99A modulated YAP1 to accelerate cell migration and invasion, and inhibited cell apoptosis in PE cells by sponging miR-134-5p. The novel regulatory network may shed light on the pathogenesis of PE.

Expression of miR-134 in Methamphetamine-induced Neuronal Injury and Its Effect on Evoked Action Potential / 中山大学学报(医学科学版)

[Objective]To investigate the expression change of miR-134 in methamphetamine(MA)-induced neuronal injury in PC12 cells and its effect on neuronal excitability and understand the pathogenesis of methamphetamine-induced neuronal injury.[Methods]PC12 cells in the logarithmic phase were divided into control group and MA group. The MA group was treated with 800μmol/L MA to establish the model of neuronal injury. The cellular injury was observed under microscope. The neuronal apoptosis was detected by Hoechst3342/PI double staining,and miR-134 expression was measured by using real-time quantitative PCR (Real time-PCR). Furthermore,we constructed miR-134 interference vector and observed its effect on evoked action potential.[Results]The cultured PC12 cells were damaged under the 800 μmol/LMA treatment ,and neurites became shorter ,the apoptotic cells were evidence. Real time-PCR showed that miR-134 expression was increased after MA treatment. Electrophysiological data showed that the evoked action potential increased after miR-134 interference.[Conclusions]High concentration of MA can induce neuronal damage and apoptosis and also increase miR-134 expression. While silence miR-134 expression can increase neuronal excitability.Our study provides an experimental basis for elucidating the possible mechanism of MA-induced neuronal injury and the role of miR-134 in neurotoxicity and neuronal excitability.

Expression of miR-134 in breast cancer and its relationship with epithelial-mesenchymal tran-sition / 临床与实验病理学杂志

Purpose To investigate the expression of miR-134 in breast carcinoma and its c1inica1 significance,and to ana1yze the as-sociation between its expression with bio-markers of epithe1ia1-mesenchyma1 transition( EMT). Methods The expression of miR-134 in 97 breast cancer samp1es was detected by in situ hybridization and the expression of E-cadherin,N-cadherin,and vimentin was de-tected by MaxVision two-step method of immunohistochemistry,to ana1yze the re1ationship between their expression and c1inicopatho1og-ica1 characteristics. Results The expression of miR-134 in breast cancer was negative1y associated with higher histo1ogica1 grade, HER-2 overexpression,1ow expression of E-cadherin as we11 as high expression of N-cadherin and vimentin. Both 1ow-expression of E-cadherin and up-expression of N-cadherin and vimentin in breast cancer were positive1y corre1ated with higher histo1ogica1 grade,1ymph node invo1vement and HER-2 overexpression,whi1e negative1y associated with the expression of ER and PR. Conclusion The expres-sion of miR-134 in breast cancer tissue is negative1y re1ated to both the ma1ignant progression and EMT,indicating that it might be a potentia1 bio-marker for breast cancer.

Expression and significance of signaling pathway of miR-134/CREB/pCREB in patients with epilepsy and in epileptic rats / 中国实验动物学报

Objective To investigate the expression of microRNA-134 ( miR-134 ) , CREB and pCREB in the temporal lobe tissue of patients and epileptic rats and to explore their roles in pathogenesis of epilepsy.Methods Tempo-ral lobe tissue samples of 14 patients with refractory epilepsy and 10 non-epileptic patients, and hippocampus and brain tis-sue samples of 42 rats were used in this study.Forty-two healthy adult male Sprague-Dawley rats were randomly divided in-to 6 epilepsy groups (24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after kindling epilepsy) and a normal control group (n=6 for all groups) .The rat model of epilepsy was generated by intraperitoneal injection of 127 mg/kg lithium chloride and 16-20 h later, 35 mg/kg pilocarpine.In the temporal lobe tissue of patients and hippocampal tissue of rats, the expression level of miR-134 was detected by real-time polymerase chain reaction.The expression levels of CREB and pCREB were de-termined by Western blot, and CREB and pCREB localization was assessed by immunohistochemistry.Results Compared with the control rats, the expression of miR-134 was significantly decreased in the temporal lobe tissue of experimental rats at 72 h,7 d,14 d, 60 d after kindling (P＜0.05),and no significant change at 24 h and 30 d after kindling (P>0.05). Expression of miR-134 in patients with refractory epilepsy was significantly lower than that of the controls ( P＜0.05 ) , while up-regulation of CREB expression was at the same time points (P＜0.05).Up-regulation of pCREB expression was at all the time points after kindling (P＜0.05).CREB and p-CREB expressions were seen in the nuclei of neurons, and significantly higher in patients with refractory epilepsy and epileptic rats.Conclusions The expression of miR-134 is sig-nificantly decreased and that of CREB and pCREB was significantly increased in the temporal lobe tissue of patients with re-fractory epilepsy and the hippocampal tissue of epileptic rats.These findings indicate that the signaling pathway of miR-134/CREB/pCREB may play an important role in the pathogenesis of epilepsy.

Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE). MATERIALS AND METHODS: Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA). RESULTS: The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. CONCLUSION: The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.