• Title/Summary/Keyword: miR-144-3p

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MiR-144-3p and Its Target Gene β-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction

  • Li, Kuo;Zhang, Junling;Ji, Chunxue;Wang, Lixuan
    • Molecules and Cells
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    • v.39 no.7
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    • pp.543-549
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    • 2016
  • MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset

  • Qi, You-Fei;Shu, Chang;Xiao, Zhan-Xiang;Luo, Ming-Yao;Fang, Kun;Guo, Yuan-Yuan;Zhang, Wen-Bo;Yue, Jie
    • Molecules and Cells
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    • v.41 no.3
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    • pp.198-206
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    • 2018
  • Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.

MicroRNA expression profiling during the suckling-to-weaning transition in pigs

  • Jang, Hyun Jun;Lee, Sang In
    • Journal of Animal Science and Technology
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    • v.63 no.4
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    • pp.854-863
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    • 2021
  • Weaning induces physiological changes in intestinal development that affect pigs' growth performance and susceptibility to disease. As a posttranscriptional regulator, microRNAs (miRNAs) regulate cellular homeostasis during intestinal development. We performed small RNA expression profiling in the small intestine of piglets before weaning (BW), 1 week after weaning (1W), and 2 weeks after weaning (2W) to identify weaning-associated differentially expressed miRNAs. We identified 38 differentially expressed miRNAs with varying expression levels among BW, 1W, and 2W. Then, we classified expression patterns of the identified miRNAs into four types. ssc-miR-196a and ssc-miR-451 represent pattern 1, which had an increased expression at 1W and a decreased expression at 2W. ssc-miR-499-5p represents pattern 2, which had an increased expression at 1W and a stable expression at 2W. ssc-miR-7135-3p and ssc-miR-144 represent pattern 3, which had a stable expression at 1W and a decreased expression at 2W. Eleven miRNAs (ssc-miR-542-3p, ssc-miR-214, ssc-miR-758, ssc-miR-4331, ssc-miR-105-1, ssc-miR-1285, ssc-miR-10a-5p, ssc-miR-4332, ssc-miR-503, ssc-miR-6782-3p, and ssc-miR-424-5p) represent pattern 4, which had a decreased expression at 1W and a stable expression at 2W. Moreover, we identified 133 candidate targets for miR-196a using a target prediction database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the target genes were associated with 19 biological processes, 4 cellular components, 8 molecular functions, and 7 KEGG pathways, including anterior/posterior pattern specification as well as the cancer, PI3K-Akt, MAPK, GnRH, and neurotrophin signaling pathways. These findings suggest that miRNAs regulate the development of the small intestine during the weaning process in piglets by anterior/posterior pattern specification as well as the cancer, PI3K-Akt, MAPK, GnRH, and neurotrophin signaling pathways.

Circulating microRNA expression profiling in young obese Korean women

  • Choi, Won Hee;Ahn, Jiyun;Um, Min Young;Jung, Chang Hwa;Jung, Sung Eun;Ha, Tae Youl
    • Nutrition Research and Practice
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    • v.14 no.4
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    • pp.412-422
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    • 2020
  • BACKGROUND/OBJECTIVES: This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20-30 years old) in Korea. SUBJECTS/METHODS: We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/㎡) and 15 obese (BMI > 25 kg/㎡) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery. RESULTS: The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324-3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = -0.5484, P = 0.0056; miR-378, r = -0.5538, P = 0.0050) and visceral fat content (miR-484, r = -0.6141, P = 0.0014; miR-378, r = -0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism. CONCLUSION: Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity.

The Relationship between Change in Obesity Indices and Change in Serum Lipids in Adult Male Workers (성인 남성 근로자에서 비만 지표의 변화와 혈청지질치 변화와의 관련성)

  • Ha, Young-Ae;Chun, Byung-Yeol;Kam, Sin;Lee, Sung-Kook;Yeh, Min-Hae
    • Journal of Preventive Medicine and Public Health
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    • v.29 no.3 s.54
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    • pp.439-449
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    • 1996
  • This study was conducted to evaluate the relationship between change in obesity indices and change in serum lipids in adult male workers. Two-hundred-eight adult male workers of an industry in Taegu city were followed-up from 1991 to 1995. Height, weight, circumferences of hip and waist, blood pressure were measured and serum lipids were analysed. Data on life style were obtained using self-administered questionnaires. Mean differences of anthropometric measurements between 1991 and 1995 were as follows: 1.63kg in weight, 3.61cm in waist circumferences, 4.23cm in hip circumferences, $0.52kg/m^2$ in BMI and -0.021 in WHR. Those of lipids were as follows; 15.09mg/dl in total cholesterol, 20.43mg/dl in triglyceride, 9.40mg/dl in HDL-cholesterol, 2.87 in MI - index (p<0.01) and 350mg/dl in LDL-cholesterol. The changed value of BMI and Katsura index were strongly correlated with that of total cholesterol(r=0.174, p<0.05), the changed value of BMI correlated with that of triglyceride(r=0.374, p<0.01) and the changed value of weight correlated with that of MI index(r=-0.173, p<0.05). The changed value of WHR was signifiantly correlated with that of total cholesterol(r=0.162, p<0.05), however, was not significantly correlated with HDL-cholesterol, LDL-cholesterol, triglyceride and MI index. The changed value of weight, BMI and Katsura index were correlated with that of triglyceride (r=0.262, p<0.01; r=0.267, p<0.01; r=0.258, p<0.01) and the changed value of MI index(r=0.143, p<0.05; r=-0.158; r=-0.144, p<0.01), adjusting the pattern of change in life style. The changed values of HDL - cholesterol and MI index between 1991 and 1995 in low WHR group were significantly higher than those in high WHR group(p<0.05, p<0.01), adjusting the baseline value of them. Similar pattern was observed when considering Katsura index. When stratifying by BMI value of 1991, in low BMI group, the changed value of HDL - cholesterol and MI index showed the same pattern as above, however that of triglyceride was statistically higher in obese group than in non obese group(p<0.05). In conclusion BMI might be a better indicator to predict serum lipids change than other obesity indices.

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miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

  • Lee, Su-Yeon;Kang, Youn-Jung;Kwon, Jinie;Nishi, Yoshihiro;Yanase, Toshihiko;Lee, Kyung-Ah;Koong, Mi Kyoung
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.3
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    • pp.194-206
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    • 2020
  • Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

Screening of key miRNAs related with the differentiation of subcutaneous adipocytes and the validation of miR-133a-3p functional significance in goats

  • Xin, Li;Hao, Zhang;Yong, Wang;Yanyan, Li;Youli, Wang;Jiangjiang, Zhu;Yaqiu, Lin
    • Animal Bioscience
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    • v.36 no.1
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    • pp.144-155
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    • 2023
  • Objective: Adipocyte differentiation is regulated by a variety of functional genes and noncoding RNAs. However, the role of miRNAs in lipid deposition of goat white adipose tissue is still unclear. Therefore, this study revealed the miRNA expression profile in goat subcutaneous adipocytes by sRNA-seq. Methods: The miRNA expressed in goat subcutaneous preadipocytes and the mature adipocytes were sequenced by sRNA-seq. The differentially expressed miRNAs (DEm) were screened and gene ontology (GO) and Kyoto encyclopedia for genes and genomes (KEGG) analyses were performed. Gain-of-function and loss-of-function combined with oil red O staining, Bodipy staining, and quantitative reverse-transcription polymerase chain reaction (qPCR) were utilized to determine the effect of miR-133a-3p on adipocyte differentiation. Results: A total of 218 DEm were screened out. The target genes of these DEm were significantly enriched in GO items such as biological regulation and in KEGG terms such as FAK signaling pathway and MAPK signaling pathway. qPCR verified that the expression trend of miRNA was consistent with miRNA-seq. The gain-of-function or loss-of-function of miR-133a-3p showed that it promoted or inhibited the accumulation of lipid droplets, and CCAAT enhancer binding protein α (C/EBPα) and C/EBPβ were extremely significantly up-regulated or down-regulated respectively (p<0.01), the loss-of-function also led to a significant down-regulation of peroxisome proliferator activated receptor gamma (PPARγ) (p<0.01). Conclusion: This study successfully identified miRNAs expression patterns in goat subcutaneous adipocytes, and functional identification indicates that miR-133a-3p is a positive regulator of the differentiation process of goat subcutaneous adipocytes. Our results lay the foundation for the molecular mechanism of lipid deposition in meat-source goats from the perspective of miRNA.

Characterization of the MicroRNA Expression Profile of Cervical Squamous Cell Carcinoma Metastases

  • Ding, Hui;Wu, Yi-Lin;Wang, Ying-Xia;Zhu, Fu-Fan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1675-1679
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    • 2014
  • Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

Resilience as a Moderator and Mediator of the Relationship between and Emotional Labor and Job Satisfaction among Nurses working in ICUs (중환자실 간호사의 감정노동과 직무만족도 관계에서 회복탄력성의 조절 및 매개효과)

  • Byeon, Mi Lim;Lee, Yun Mi;Park, Hyo jin
    • Journal of Korean Critical Care Nursing
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    • v.12 no.3
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    • pp.24-34
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    • 2019
  • Purpose : The purpose of this study was to identify the moderating and mediating effects of resilience in the relationship between emotional labor and job satisfaction among nurses working in intensive care units (ICUs). Method : The participants were 144 ICU nurses from three university hospitals. Data were collected using structured questionnaires and analyzed by t-test, ANOVA, $Scheff{\acute{e}}$ test, Pearson correlation coefficients, and multiple regression analysis, using SPSS 25.0. The mediating effect of resilience in the relationship between emotional labor and job satisfaction was analyzed by multiple regression analysis according to Baron and Kenny's procedure. Results : Statistically significant negative correlations were found between emotional labor and resilience (r=-.21, p<.014) and between emotional labor and job satisfaction (r=-.34, p<.001). A significant positive correlation was found between resilience and job satisfaction (r=.31 p<.001). A partial mediating effect by resilience was found between emotional labor and job satisfaction (Z=-2.11, p=.034), but no moderating effect was found. Conclusion : To improve the job satisfaction of ICU nurses, evaluation of their emotional labor, resilience, and interventions are necessary to alleviate emotional labor and improve resilience.

The Relationship between Personality Types, Learning Style, and Academic Achievement in First Year Nursing Students (간호학과 신입생의 성격유형, 학습스타일과 학업성취도의 관계)

  • Yun, HeeJang;Kwak, EunMi;Kwon, SunYoung
    • The Journal of the Convergence on Culture Technology
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    • v.5 no.2
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    • pp.247-255
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    • 2019
  • This study was conducted to explore the correlation between the personality types and learning styles and academic achievement in first year nursing students. 144 students were sampled in first year nursing sstudents. Data were collected from March 6 to May 18 2018. Results analysis was performed using SPSS win version of frequency, mean and standard deviation, t-test, ANOVA, Chi-square test, Pearson correlation. The personality types of nursing students in this study were 58.3% of Extrovert type, 41.7% of Introvert type, 33.3% of Sensing, 66.7% of Intuition type, 22.2% of Thinking, 77.8% of Feeling, 50.7% of Judging type, and 49.3% of Perceiving type. The average academic achievement of female students was 3.51 points, higher than the average of 3.17 for male students (t=-3.277, p<.001). The average academic achievement of Introvert type was found to be higher than the average of Extrovert type (t=3.541, p<.001). Learning styles by personality type showed a statistically significant difference between the judging type and the other personality types (${\chi}^2=18.409$, p<.001). There was a significant amount of correlation between gender and TF index (r=.209, p<.05), gender and academic achievement (r=.265, p<.01), JP index and learning styles (r=.262, p<.01, EI index and academic achievement (r=.285, p<.01). The development and utilization of teaching-learning methods suitable for individuals will be required based on the results of personality types, learning styles and academic achievement in first year nursing students identified through this study.