MicroRNA expression profile in RAW264·7 macrophage cells exposed toEchinococcus multilocularismetacestodes

Parasitology ◽  
2017 ◽  
Vol 145 (3) ◽  
pp. 416-423 ◽  
Author(s):  
XIAOLA GUO ◽  
YADONG ZHENG

SUMMARYMicroRNAs (miRNAs) are short noncoding RNAs, involved in the regulation of parasite diseases. However, a role of miRNAs inEchinococcus multilocularisinfection remains largely unknown. In this study, we first found the expression levels of key genes involved in miRNA biogenesis and function, includingAgo2,Xpo5,Tarbp2andDgcR8, were obviously altered in the macrophage RAW264·7 cells exposed toE. multilocularismetacestodes. Compared with the control, 18 and 32 known miRNAs were found to be differentially expressed (P< 0·05 and fold change >2) in the macrophages exposed toE. multilocularismetacestodes for 6 and 12 h, respectively. Among these, several are known to be involved in regulating cytokine activities and immune responses. Quantitative real-time polymerase chain reaction results showed that the expression of nine selected miRNAs was consistent with the sequencing data at each treatment time points. Moreover, there were statistically significant correlations between the expression levels of miRNAs and their corresponding targeted genes. Our data give us some clues to pinpoint a role of miRNAs in the course of infection and immunity ofE. multilocularis.

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Jian Zhou ◽  
Xiujuan Duan ◽  
Jibing Wang ◽  
Yunhong Feng ◽  
Jiangyong Yuan

Objective. This study is aimed at determining the expression and function of the GASL1 and PI3K/AKT pathways in isoproterenol- (ISO-) induced heart failure (HF). To determine the moderating effect of valsartan (VAL) on the progression of ISO-induced HF and to elucidate the related mechanism. Materials and Methods. First, in in vivo experiment, we examined the effect of VAL on cardiac function in rats with ISO-induced HF. Similarly, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of VAL on ISO-treated rat primary cardiomyocytes. Then, si-GASL1-transfected primary cardiomyocytes were constructed and Ad-si-GASL1 was injected through rat tail vein to achieve the effect of lowering GASL1 expression, so as to investigate the role of GASL1 in VAL’s treatment of ISO-induced HF. Results. In ISO-induced HF rat models, the GASL1 decreased while PI3K and p-AKT expressions were abnormally elevated and cardiac function deteriorated, and VAL was able to reverse these changes. In primary cardiomyocytes, ISO induces apoptosis of cardiomyocytes, and expression of GASL1 decreased while PI3K and p-AKT were abnormally elevated, which can be reversed by VAL. The transfection of primary cardiomyocytes with si-GASL1 confirmed that GASL1 affected the expression of PI3K, p-AKT, and the apoptosis of primary cardiomyocytes. Rat myocardium injected with Ad-si-GASL1 was found to aggravate the cardiac function improved by VAL. Conclusions. This study was the first to confirm that VAL improves ISO-induced HF by regulating the PI3K/AKT pathway through GASL1. And this study demonstrated a significant correlation between HF, VAL, GASL1, and the PI3K/AKT pathway.


2019 ◽  
Vol 20 (15) ◽  
pp. 3771 ◽  
Author(s):  
Eun Ju Ko ◽  
Eo Jin Kim ◽  
Jung Oh Kim ◽  
Jung Hoon Sung ◽  
Han Sung Park ◽  
...  

Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of microRNAs (miRNAs) are well-known regulators of thrombosis and thrombolysis, and mutations in miRNA biogenesis genes, such as DICER1, DROSHA have been implicated in miRNA synthesis and function. We investigated the genetic association between polymorphisms in four miRNA biogenesis genes, DICER1 rs3742330A > G, DROSHA rs10719T > C, RAN rs14035C > T and XPO5 rs11077A > C, and VTE in 503 Koreans: 300 controls and 203 patients. Genotyping was assessed with polymerase chain reaction-restriction fragment length polymorphism assays. We detected associations between polymorphisms in RAN and XPO5 and VTE prevalence (RAN rs14035CC + CT versus TT: p = 0.018; XPO5 rs11077AA + AC versus CC: p < 0.001). Analysis of allele combinations of all four polymorphisms (DICER1, DROSHA, RAN, XPO5) revealed that A-T-T-A was associated with decreased VTE prevalence (p = 0.0002), and A-T-C-C was associated with increased VTE prevalence (p = 0.027). Moreover, in subjects with provoked VTE, the DROSHA rs10719T > C, polymorphism was associated with increased disease prevalence (TT versus TC + CC: p < 0.039). Our study demonstrates that RAN and XPO5 polymorphisms are associated with risk for VTE in Korean subjects.


2011 ◽  
Vol 2011 ◽  
pp. 1-27 ◽  
Author(s):  
Kemal Ugur Tufekci ◽  
Meryem Gulfem Oner ◽  
Sermin Genc ◽  
Kursad Genc

MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene expression. miRNAs control protein synthesis by targeting mRNAs for translational repression or degradation at the posttranscriptional level. These noncoding RNAs are endogenous, single-stranded molecules approximately 22 nucleotides in length and have roles in multiple facets of immunity, from regulation of development of key cellular players to activation and function in immune responses. Recent studies have shown that dysregulation of miRNAs involved in immune responses leads to autoimmunity. Multiple sclerosis (MS) serves as an example of a chronic and organ-specific autoimmune disease in which miRNAs modulate immune responses in the peripheral immune compartment and the neuroinflammatory process in the brain. For MS, miRNAs have the potential to serve as modifying drugs. In this review, we summarize current knowledge of miRNA biogenesis and mode of action and the diverse roles of miRNAs in modulating the immune and inflammatory responses. We also review the role of miRNAs in autoimmunity, focusing on emerging data regarding miRNA expression patterns in MS. Finally, we discuss the potential of miRNAs as a disease marker and a novel therapeutic target in MS. Better understanding of the role of miRNAs in MS will improve our knowledge of the pathogenesis of this disease.


2020 ◽  
Author(s):  
Ying Wang ◽  
Jidong Ru ◽  
Meng Xianglian

Abstract BackgroundSNPs within pre-miRNA regions play a significant role in miRNA generation, processing and function by different molecular mechanisms and are thought to be major contributors to the variations in phenotypes and diseases. Therefore, whole-genome analysis of how SNPs affect mature miRNA biogenesis is important for precision medicine. ResultsIn this study, aiming to analyze the role of SNPs in mature miRNA biogenesis genome-wide, we constructed a SNP-pre-miRNA database, named miRSNPBase, consisting of 886 pre-miRNAs and 2640 SNPs based on the latest data. Then, we identified 10574 SNP-pre-miRNAs based on 886 pre-miRNAs and their associated 2640 SNPs, and we performed genome-wide association analyses to identify isoform miRNAs (isomiRs) based on miRFind that are associated with the mechanism of SNPs affecting miRNA maturation. A total of 4235 nor-SNP-pre-miRNAs based on 480 nor-pre-miRNAs and 1250 nor-SNPs were identified. We analyzed the effects of SNP type, SNP location and SNP-mediated free energy change during mature miRNA biogenesis and found that they are closely related to mature miRNA biogenesis. In addition, the MAF distribution of the iso-pre-miRNAs and nor-SNPs was analyzed based on the 1000 Genomes Project. The results demonstrated that individuals who contained the iso-SNPs were in the minority, and those who contained the nor-SNPs were in the majority. Notably, to verify our method and identify important biomarkers, we identified isomiRs and iso-SNPs in 18 GBR individuals of European origin. In the results, 209 iso-pre-miRNA candidates and 71 verified iso-pre-miRNAs of the 18 GBR samples were identified, and 2667 isomiRs of 209 pre-miRNAs were verified by miRNA sequencing data.ConclusionsOur results clearly indicated that SNPs that altered the mature miRNA splicing mechanism and led to the production of isomiRs, were closely related to and affected normal life processes, and led to epigenetic changes and diseases.


2018 ◽  
Vol 33 (4) ◽  
pp. 407-414 ◽  
Author(s):  
Lin-Lin Cao ◽  
Changzheng Du ◽  
Hangqi Liu ◽  
Lin Pei ◽  
Li Qin ◽  
...  

Objective: Lysine-specific demethylase 2A (KDM2A), a specific H3K36me1/2 demethylase, has been reported to be closely associated with several types of cancer. In this study, we aimed to investigate the expression and function of KDM2A in colorectal adenocarcinoma. Methods: A total of 215 colorectal adenocarcinoma specimens were collected, and then subjected to immunohistochemistry assay to evaluate the expression levels of KDM2A, cyclin D1 and other proteins in colorectal adenocarcinoma tissues. Real-time polymerase chain reaction, Western blot, and other molecular biology methods were used to explore the role of KDM2A in colorectal adenocarcinoma cells. Results: In this study, we report that the expression level of KDM2A is high in colorectal adenocarcinoma tissues, and this high expression promotes the proliferation and colony formation of colorectal adenocarcinoma cells, as demonstrated by KDM2A knockdown experiments. In addition, the expression of KDM2A is closely associated with cyclin D1 expression in colorectal adenocarcinoma tissues and cell lines. Conclusions: Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Zhang ◽  
Hao Niu ◽  
Ping Yang ◽  
Jie Ma ◽  
Bao-Ying Yuan ◽  
...  

Abstract Background Early screening and intervention therapies are crucial to improve the prognosis of hepatocellular carcinoma (HCC) patients with bone metastasis. We aimed to identify serum lncRNA as a prediction biomarker in HCC bone metastasis. Methods The expression levels of lnc34a in serum samples from 157 HCC patients were detected by quantitative real-time polymerase chain reaction (PCR). Univariate analysis and multivariate analysis were performed to determine statistically significant variables. Results Expression levels of lnc34a in serum from HCC patients with bone metastasis were significantly higher than those without bone metastasis. The high expressions of lnc34a, vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage were associated with bone metastasis by analysis. Moreover, lnc34a expression was specifically associated with bone metastasis rather than lung or lymph node metastasis in HCC. Conclusions High serum lnc34a expression was a independent risk factor for developing bone metastasis in HCC.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Raquel Weber ◽  
Ana Paula Santin Bertoni ◽  
Laura Walter Bessestil ◽  
Ilma Simoni Brum ◽  
Tania Weber Furlanetto

Goiter is more common in women, suggesting that estrogen could be involved in its physiopathology. The presence of classical estrogen receptors (ERαand ERβ) has been described in thyroid tissue, suggesting a direct effect of estrogen on the gland. A nonclassic estrogen receptor, the G-protein-coupled estrogen receptor (GPER1), has been described recently in several tissues. However, in goiter, the presence of this receptor has not been studied yet. We investigated GPER1 gene and protein expressions in normal thyroid and goiter using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. In normal thyroid (n=16) and goiter (n=19), GPER1 gene was expressed in all samples, while GPER1 protein was expressed in all samples of normal thyroid (n=15) but in only 72% of goiter samples (n=13). When comparing GPER1 gene and protein levels in both conditions, gene expression and protein levels were higher in normal thyroid than in goiter, suggesting a role of this receptor in this condition. Further studies are needed to elucidate the role of GPER1 in normal thyroid and goiter.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Ming Liu ◽  
Zikun Xie ◽  
Guang Sun ◽  
Liujun Chen ◽  
Dake Qi ◽  
...  

Abstract Background Osteoarthritis (OA) is the most prevalent form of arthritis and the major cause of disability and overall diminution of quality of life in the elderly population. Currently there is no cure for OA, partly due to the large gaps in our understanding of its underlying molecular and cellular mechanisms. Macrophage migration inhibitory factor (MIF) is a procytokine that mediates pleiotropic inflammatory effects in inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, data on the role of MIF in OA is limited with conflicting results. We undertook this study to investigate the role of MIF in OA by examining MIF genotype, mRNA expression, and protein levels in the Newfoundland Osteoarthritis Study. Methods One hundred nineteen end-stage knee/hip OA patients, 16 RA patients, and 113 healthy controls were included in the study. Two polymorphisms in the MIF gene, rs755622, and -794 CATT5-8, were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and PCR followed by automated capillary electrophoresis, respectively. MIF mRNA levels in articular cartilage and subchondral bone were measured by quantitative polymerase chain reaction. Plasma concentrations of MIF, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) were measured by enzyme-linked immunosorbent assay. Results rs755622 and -794 CATT5-8 genotypes were not associated with MIF mRNA or protein levels or OA (all p ≥ 0.19). MIF mRNA level in cartilage was lower in OA patients than in controls (p = 0.028) and RA patients (p = 0.004), while the levels in bone were comparable between OA patients and controls (p = 0.165). MIF protein level in plasma was lower in OA patients than in controls (p = 3.01 × 10−10), while the levels of TNF-α, IL-6 and IL-1β in plasma were all significantly higher in OA patients than in controls (all p ≤ 0.0007). Multivariable logistic regression showed lower MIF and higher IL-1β protein levels in plasma were independently associated with OA (OR per SD increase = 0.10 and 8.08; 95% CI = 0.04–0.19 and 4.42–16.82, respectively), but TNF-α and IL-6 became non-significant. Conclusions Reduced MIF mRNA and protein expression in OA patients suggested MIF might have a protective role in OA and could serve as a biomarker to differentiate OA from other joint disorders.


2018 ◽  
Vol 16 ◽  
pp. 205873921876729
Author(s):  
An Wan ◽  
Daodong Liu

Osteoporosis is a chronic multifactorial disease characterized by deterioration of bone mass and is vulnerable to bone fracture. Plasminogen activator inhibitor-1 (PAI-1) is an important molecule for maintenance of optimum bone mass. Several single-nucleotide polymorphisms (SNPs) in PAI-1 have been reported to alter PAI-1 expression and/or the translational level. In this report, we explored the possible role of common PAI-1 gene polymorphisms on predisposition to osteoporosis in a Chinese cohort. A total of 364 post-menopausal Chinese women diagnosed of having osteoporosis and 350 healthy females hailing from similar areas were enrolled in this study. Five common SNPs (−844G > A, −6754G/5G, +43G > A, +9785G > A and +11053T > G) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Relative expression of PAI-1 mRNA and plasma PAI-1 levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Prevalence of homozygous mutant (5G/5G) and minor allele (5G) of PAI-1 (−675 4G/5G) polymorphism was significantly more frequent in patients than in healthy controls (5G/5G: P < 0.0001, odds ratio (OR) = 3.18; 5G: P < 0.0001, OR = 1.65). Both plasma PAI-1 and relative mRNA expression levels were significantly lower in patients compared to healthy controls. Interestingly, the quantity of plasma PAI-1 and mRNA expression was correlated with PAI-1 (−675 4G/5G) polymorphism: subjects with 4G/4G genotype had elevated PAI-1 in comparison to homozygous mutant, and displayed lower quantity of PAI-1 protein and mRNA values. PAI-1 (−675 4G/5G) mutant is associated with susceptibility to development of osteoporosis in post-menopausal Chinese women. Furthermore, this variant in the promoter region alters plasma protein levels and relative expression of PAI-1.


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