• Title/Summary/Keyword: miR-374a

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MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway

  • Long, Zi-Wen;Wu, Jiang-Hong;Hong, Cai;Wang, Ya-Nong;Zhou, Ye
    • Molecules and Cells
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    • v.41 no.6
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    • pp.532-544
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    • 2018
  • Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

  • Li, Jian-Yi;Zhang, Yang;Zhang, Wen-Hai;Jia, Shi;Kang, Ye;Tian, Rui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1715-1720
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    • 2013
  • Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.

miR-374 promotes myocardial hypertrophy by negatively regulating vascular endothelial growth factor receptor-1 signaling

  • Lee, Jong Sub;Song, Dong Woo;Park, Jei Hyoung;Kim, Jin Ock;Cho, Chunghee;Kim, Do Han
    • BMB Reports
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    • v.50 no.4
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    • pp.208-213
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    • 2017
  • Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGF-receptor-1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3'-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway.

Profiling of Salivary Exosomal Micro RNAs in Burning Mouth Syndrome Patients

  • Kim, Kyun-Yo;Byun, Jin-Seok;Jung, Jae-Kwang;Choi, Jae-Kap
    • Journal of Oral Medicine and Pain
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    • v.44 no.1
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    • pp.25-30
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    • 2019
  • Purpose: The exact causes of burning mouth syndrome (BMS) is unclear so far. There are many studies to elucidate the relation between oral disease and genetic predisposition. In this study, we first tried to investigate salivary exosomal genetic components that could play an important role for diagnosing and elucidating the progression of BMS. Methods: We compared salivary exosomal micro RNAs (miRNAs) of BMS Patients to those of control using next generation sequencing (NGS). Unstimulated whole saliva from 15 patients with BMS and 10 control subjects were divided into two sets. Isolated exosomes and their total RNAs were subject to NGS for the screening of miRNAs. Results: There were up-regulated 10 exosomal miRNAs (hsa-miR-1273h-5p, hsa-miR-1273a, hsa-miR-1304-3p, hsa-miR-4449, hsa-miR-1285-3p, hsa-miR-6802-5p, hsa-miR-1268a, hsa-miR-1273d, hsa-miR-1273f, and hsa-miR-423-5p) and down-regulated 18 exosomal miRNAs (hsa-miR-27b-3p, hsa-miR-16-5p, hsa-miR-186-5p, hsa-miR-142-3p, hsa-miR-141-3p, hsa-miR-150-5p, hsa-miR-374a-5p, hsa-miR-93-5p, hsa-miR-29c-3p, hsa-miR-29a-3p, hsa-miR-148a-3p, hsa-miR-22-3p, hsa-miR-27a-3p, hsa-miR-424-5p, hsa-miR-19b-3p, hsa-miR-99a-5p, hsa-miR-548d-3p, and hsa-miR-19a-3p) in BMS patients comparing with those of control subjects. Conclusions: We show that there are 28 differential expression of miRNAs between the patients with BMS and those of control subjects. The specific function of indicated miRNAs should be further elucidated.

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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Screening for the 3' UTR Polymorphism of the PXR Gene in South Indian Breast Cancer Patients and its Potential role in Pharmacogenomics

  • Revathidevi, Sundaramoorthy;Sudesh, Ravi;Vaishnavi, Varadharajan;Kaliyanasundaram, Muthukrishnan;MaryHelen, Kilyara George;Sukanya, Ganesan;Munirajan, Arasambattu Kannan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3971-3977
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    • 2016
  • Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

Synthesis and X-ray Crystallographic Characterization of p-Diacetylcalix[4]arene

  • Young Ja Park;Kwanghyun No;Jung Mi Shin
    • Bulletin of the Korean Chemical Society
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    • v.12 no.5
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    • pp.525-529
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    • 1991
  • A simple route is described for the selective functionalization of calixarene at the para positions of phenyl rings. Calix[4]arene tetraacetate 2, obtained from the treatment of calix[4]arene with acetic anhydride, undergoes Fries rearrangement to yield the diametrically para substituted p-diacetylcalix[4]arene 3 in 80% yield. The crystal and molecular strucutre has been determined by X-ray diffraction method. The crystals are orthorhombic, space group Pna21, with a = 11.121 (3), b = 10.374 (3), c = 21.690 (6) $\AA$ and Z = 4. The structure was solved by direct method and refined by full-matrix least-squares methods to final R of 0.036 for 1795 observed reflections. Each hydroxyl hydrogen atom is disordered over two positions. The macrocycle exists in the cone conformation which is determined by the strong circular intramolecular flip-flop type hydrogen bonds of phenolic OH, while crystal packing effects of the diametrically para-acetyl substituents seem to be responsible for the distortion of the cone conformation.

A Study on Correlation of Sensory Processing ability With Feeding of Preterm Infants and Toddlers (조산으로 출생한 영유아의 감각처리능력과 섭식의 상관관계)

  • Kim, Mi-Su;Kim, Kyeong-Mi;Chang, Moon-Young;Hong, Eunkyoung
    • The Journal of Korean Academy of Sensory Integration
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    • v.17 no.2
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    • pp.31-40
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    • 2019
  • Purpose : The purpose of this study was to compare the difference between preterm infants and toddlers (PT) and full-term infant and toddler (FT) of sensory processing ability, feeding as well as investigate the correlation of sensory processing ability with feeding of preterm infants and toddlers. Methods : The subjects of a study were 107 including 51 PT and 56 FT. Infant/Toddler Sensory Profile 2 (ITSP 2) was used to assess sensory processing ability. The Behavioral Pediatrics Feeding Assessment (BPFAS) was used to assess feeding behavior. The collected data were analyzed by using SPSS 21.0. Independent sample t-test was used in order to compare the difference between PT group and FT group. Pearson correlation analysis was used in order to investigate the correlation of sensory processing ability with feeding of preterm infants and toddlers. Results : There was a significant difference in sensory sensitivity and oral sensory processing between with PT group and FT group (p<0.05). There was a significant difference in feeding behavior between with PT group and FT group (p<.05). In PT group, there are positive correlations of sensory avoidance (r=.443) and sensory sensitivity (r=.374) with feeding frequency. General behavior (r=.390) and oral sensory processing (r=.513) showed a positive correlation with feeding frequency. In addition, oral sensory processing (r=.529) showed a positive correlation with feeding problem. Conclusion : It is proved that the interrelationship of sensory processing ability with feeding and of preterm infants and toddlers. And it is meaningful to recognize significance of sensory processing characteristics to comprehend feeding and of preterm infants and toddlers.

Evaluation of the Interstitial Cystitis Symptom Index and Problem Index-Korean Version (한국판 간질성 방광염 증상지수/문제지수(ICSI/ICPI-K)의 평가)

  • Son, Haeng-Mi;Kim, Jeung-Im
    • Women's Health Nursing
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    • v.14 no.4
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    • pp.290-296
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    • 2008
  • Purpose: The O'Leary Symptom Index and Problem Index(ICSI/ICPI) have been used widespread in clinical studies and research. This research was aimed to determine the reliability and validity of the ICSI/ICPI-K that was translated into Korean. Methods: The research design was a methodological study to test the measurements. Subjects were 301 elderly women in Seoul, Chungnam and Gyungbuk. They were recruited through a formal announcement and they responded after informed consent. Data was analyzed with SPSS 15.0. The internal consistency was assessed by Cronbach's alpha coefficient and the criterion validity was assessed by Pearson correlation with the Geriatric Depression Scale(GDS) and inter-subscales. Results: The elderly women were on average 74.3 years old. As to the reliability of the scale, ICSI/ICPI-K had a Cronbach alpha of .832. In addition, the results showed that ICSI/ICPI-K was valid through the Pearson correlation. That is, the ICSI-K and ICPI-K had a significant relationship with GDS(r=.295; r=.374, respectively) and strong correlations of subscale to subscale(ICSI-K & ICPI-K: r=.676). The most common symptom of the lower urinary tract by the ICSI/ICPI-K was nocturia 249(83.3%) followed by frequency 187(62.8%), urgency 148(49.8%). and pelvic pain 71(23.9%) in the elderly women. Conclusion: We can conclude that the ICSI/ICPI-K is reliable and valid in Korean elderly women. It needs to be evaluated in the clinical area.

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