• Molecules and Cells
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• 제39권7호
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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.

• Molecules and Cells
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• 제41권3호
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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.

• Journal of Animal Science and Technology
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• 제63권4호
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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.

• Nutrition Research and Practice
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• 제14권4호
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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.

• Journal of Preventive Medicine and Public Health
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• 제29권3호
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• pp.439-449
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• 1996

성인 남성 근로자들에 있어서 비만지표의 변화와 혈청지질치 변화와의 관련성을 평가하기 위하여, 대구시에 소재한 1개 회사의 남성 근로자 208명을 연구 대상자로 선정하였다. 1995년 7월에 신장, 체중, 허리둘레, 엉덩이둘레를 재고 혈압을 측정하였으며, 혈청 총 콜레스테롤, 중성지방, HDL-콜레스테롤 등을 검사하고 LDL-콜레스테롤, 심근경색지수를 계산하였다. 이를 1991년도에 검사된 기초 자료들과 비교하였다. 1. 4년간 체중이 1.63kg, 허리둘레가 3.61cm, 엉덩이둘레가 4.23cm, BMI가 $0.52kg/m^2$, Katsura 지수는 0.02만큼 유의하게 증가했지만, 허리 엉덩이둘레비는 0.021만큼 유의한 감소가 있었다(p<0.01). 총 콜레스테롤은 15.09mg/이, 중성지방 20.43mg/dl, HDL-콜레스테롤 9.40mg/dl, 그리고 심근경색지수는 2.87mg/dl 만큼 유의하게 증가하였다. (p<0.01). LDL-콜레스테롤은 3.50mg/dl 만큼 증가하였으나 유의하지는 않았다. 2. BMI 변화 및 Katsura 지수의 변화와 총 콜레스테롤의 변화(r=0.174, p<0.05), BMI 변화와 중성지방의 변화(r=0.374, p<0.01), 그리고 체중의 변화와 심근경색지수의 변화(r=-0.173, p<0.05)가 상대적으로 강한 상관성을 보였다. 허리 엉덩이둘레비 변화는 총 콜레스테롤 변화량과 양의 상관관계(r=0.162, p<0.05)를 보였지만 다른 혈청지질치들과는 유의한 관련성이 없었다. 3. 생활습관의 변화를 보정하고도 중성지방은 체중 (r=0.262, p<0.01), BMI(r=0.267, p<0.01) Katsura 지수(r=0.258, p<0.01)와 유의한 관련성이 있었다. 심근경색지수의 변화는 체중(r=-0.143, p<0.05), BMI(r=-0.158, p<0.05), Katsura 지수(r=-0.144, p<0.05)와 유의한 음의 관련성이 있었다. 이 중 BMI가 가장 큰 상관계수 값을 보였다. 4. 1991년의 허리 엉덩이둘레비로 분류한 경우, 상체형 비만군이 그렇지 않은 군에 비해 HDL-콜레스테롤과 심근경색지수의 증가폭이 유의하게 더 낮았다(p<0.05). Katsura 지수의 경우도 유사한 결과를 보였다. BMI로 분류한 경우에도 역시 비만군이 그렇지 않은 군에 비해 HDL-콜레스테롤, 심근경색지수 값들의 증가폭이 유의하게 낮았다(p<0.05 또는 p<0.01). 중성지방은 BMI로 분류한 경우 비만한 군의 증가폭이 유의하게 높았다(p<0.05). 이상의 결과로 보아, 성인 남성 근로자들에서 혈청 지질치 변화에 대한 비만도의 지표로는 BMI가 허리 엉덩이둘레비나 Katsura 지수보다 더 적절할 것으로 생각된다.

• Clinical and Experimental Reproductive Medicine
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• 제47권3호
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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.

• Animal Bioscience
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• 제36권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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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.

• 중환자간호학회지
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• 제12권3호
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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.

• 문화기술의 융합
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• 제5권2호
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• pp.247-255
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• 2019

본 연구는 간호학과 신입생들의 성격유형과 학습스타일, 학업성취도 간의 상관성을 탐구하기 위해 시행되었다. 간호학과 신입생 144명을 대상으로 2018년 3월 6일부터 5월 18일 까지 자료를 수집하였다. 결과 분석은 빈도와 백분율, 평균 및 표준편차, t-test와 ANOVA, Chi-square test 그리고 Pearson correlation coefficient로 확인하였다. 연구 대상자의 성격유형은 외향적 성향(58.3%)이 내향적 성향 보다 많았으며 감각적 성향(66.7%)과 감정형(77.8%)이 직관적 성향과 사고형 보다 많았고 판단형(50.7%)이 인지형 보다 많았다. 학업성취도는 여학생이 남학생 보다 높았고(t=3.277, p<.001), 내향적 성향이 외향적 성향 보다 높았다(t=3.541, p<.001). 성격유형별 학습스타일의 차이는 판단형이 다른 성격 유형간에 통계적으로 유의미한 차이를 보였다(${\chi}^2=18.409$, p<.001). 성별과 TF지표(r=.209, p<.05), 성별과 학업성취도(r=.265, p<.01), JP지표와 학습스타일(r=.262, p<.01), EI지표와 학업성취도(r=.285, p<.01) 사이에 유의한 양의 상관관계가 나타났다. 본 연구를 통해 확인된 간호학과 신입생의 성격유형, 학습스타일, 학업성취도 결과를 바탕으로 개인에게 적합한 교수-학습법의 개발 및 활용이 필요할 것이다.