• 제목/요약/키워드: Micro-Targeting

검색결과 136건 처리시간 0.02초

Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation

  • Lee, Ji Yoon;Kim, MyungJoo;Heo, Hye-Ryeon;Ha, Kwon-Soo;Han, Eun-Taek;Park, Won Sun;Yang, Se-Ran;Hong, Seok-Ho
    • Molecules and Cells
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    • 제41권11호
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    • pp.971-978
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    • 2018
  • The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.

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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    • 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.

MicroRNA-27 Promotes Odontoblast Differentiation via Wnt1 Signaling

  • Cho, Ji-Ho;Kim, Su-Gwan;Park, Byung-Sun;Go, Dae-San;Park, Joo-Cheol;Kim, Do Kyung
    • International Journal of Oral Biology
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    • 제40권4호
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    • pp.197-204
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    • 2015
  • MicroRNA (miRNA, miR) is essential in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNA in odontoblastic cell differentiation is still unclear. In this study, we examined the molecular mechanism of miR-27-mediated regulation of odontoblast differentiation in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. The results of the present study demonstrated that the miR-27 expression increases significantly during MDPC-23 odontoblastic cell differentiation. Furthermore, miR-27 up-regulation promotes the differentiation of MDPC-23 cells and accelerates mineralization without cell proliferation. The over-expression of miR-27 significantly increased the expression levels of Wnt1 mRNA and protein. In addition, the results of target gene prediction revealed that Wnt1 mRNA has an miR-27 binding site in its 3'UTR, and is increased by miR-27. These results suggested that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting Wnt1 signaling. Therefore, miR-27 is a critical odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in dental medicine.

Hypoxia-induced miR-1260b regulates vascular smooth muscle cell proliferation by targeting GDF11

  • Seong, Minhyeong;Kang, Hara
    • BMB Reports
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    • 제53권4호
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    • pp.206-211
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    • 2020
  • Vascular smooth muscle cells (VSMCs) are a unique cell type that has unusual plasticity controlled by environmental stimuli. As an abnormal increase of VSMC proliferation is associated with various vascular diseases, tight regulation of VSMC phenotypes is essential for maintaining vascular homeostasis. Hypoxia is one environmental stress that stimulates VSMC proliferation. Emerging evidence has indicated that microRNAs (miRNAs) are critical regulators in the hypoxic responses of VSMCs. Therefore, we previously investigated miRNAs modulated by hypoxia in VSMCs and found that miR-1260b is one of the most upregulated miRNAs under hypoxia. However, the mechanism that underlies the regulation of VSMCs via miR-1260b in response to hypoxia has not been explored. Here we demonstrated that hypoxia-induced miR-1260b promotes VSMC proliferation. We also identified growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, as a novel target of miR-1260b. miR-1260b directly targets the 3'UTR of GDF11. Downregulation of GDF11 inhibited Smad signaling and consequently enhanced the proliferation of VSMCs. Our findings suggest that miR-1260b-mediated GDF11-Smad-dependent signaling is an essential regulatory mechanism in the proliferation of VSMCs, and this axis is modulated by hypoxia to promote abnormal VSMC proliferation. Therefore, our study unveils a novel function of miR-1260b in the pathological proliferation of VSMCs under hypoxia.

Molecular Imaging of Arthritis in the Angiogenic Vasculature Using A 123I-Vascular Endothelial Growth Factor Receptor Antibody

  • Kim, Sung-Min;Choi, Na-Eun;Song, Young-Kyu;Cho, Gyung-Goo;Bang, Jeong-Kyu;Kim, Sang-Mi;Lee, Sang-Hoon;Ryu, Eun-Kyoung
    • Bulletin of the Korean Chemical Society
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    • 제33권6호
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    • pp.1890-1894
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    • 2012
  • Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been implicated in the pathogenesis of rheumatoid arthritis, which is angiogenesis dependent. Antibody-based molecular imaging improves targeting, and antibody radiolabeling is useful for monitoring biological events $in$ $vivo$ $via$ PET or SPECT. We investigated the potential of molecular imaging to diagnose arthritis with VEGFR-2 $in$ $vivo$. The $^{123}I$-VEGFR-2 antibody was prepared by the iodogen tube method. The radioligand was injected into arthritic mice, and micro SPECT/CT was performed. The arthritic mice were examined by 4.7-T MRI and immunohistochemistry. The $^{123}I$-VEGFR-2 antibody showed high uptake in the arthritic region at 1 h postinjection on SPECT/CT but no uptake in the control animals after radioligand injection. In MR images, the arthritic tissue of the mice was correlated with regions labeled by the $^{123}I$-VEGFR-2 antibody. Immunohistochemical localization showed markedly increased expression of VEGFR-2 in the endothelial cells, fibroblasts, and macrophages of the arthritic mice.

미량 및 신종유해물질의 국내 방류 환경에서의 위해성 평가: 환경부 지정 1순위 80종 대상으로 (Risk Assessment of Micro and Emerging Contaminants in Domestic Effluent Environment: Targeting on 80 First-class substances assigned by Ministry of Environment)

  • 이재엽;박새롬;김일호
    • 한국물환경학회지
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    • 제37권6호
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    • pp.501-509
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    • 2021
  • In 2018, total 263 micro and emerging contaminants were selected as target substances by the Ministry of Environment, and 80 of them were first-class substance including endocrine disruptors, residual Pharmaceuticals and Personal Care Products (PPCPs), residual organic pollutants, pesticides and heavy metals. In this study, in order to evaluate the Hazard Quotient (HQ) of the 80 types in the domestic water environment the concentration of discharged effluent and nearby water environment reported by Korean institutes since 2010 was investigated. There were 45 substances reported to be detected, and Measurement Environment Concentration (MEC) were obtained by collectively converting them into water environment concentration. For biotoxicity, half maximal Effective Dose (EC50) to Daphnia magna, a water fleas species widely adopted in Material Safety Data Sheet (MSDS) was applied. As for the biotoxicity level, the Predicted No-Effect Concentration (PNEC) was obtained by applying the Assessment Factor (AF) and the HQ was derived by dividing it from the MEC. As a result of calculating the HQ, more than 1 substances were Cabamazepine, Mefenamic acid, Acetaminophen, Ibuprofen, Nonylphenol, Nickel, Erythromycin, Acetylslic acid, etc. Meanwhile, perfluorinated compounds were identified as hazardous substances in the water env ironment, with 5 out of 14 species included in the 20 ranks of first-class substance.

Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression

  • Hu, Yanchao;Zhang, Chunyan;Fan, Yajie;Zhang, Yan;Wang, Yiwen;Wang, Congxia
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권6호
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    • pp.519-530
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    • 2022
  • Recent research indicates that lactate promotes the switching of vascular smooth muscle cells (VSMCs) to a synthetic phenotype, which has been implicated in various vascular diseases. This study aimed to investigate the effects of lactate on the VSMC phenotype switch and the underlying mechanism. The CCK-8 method was used to assess cell viability. The microRNAs and mRNAs levels were evaluated using quantitative PCR. Targets of microRNA were predicted using online tools and confirmed using a luciferase reporter assay. We found that lactate promoted the switch of VSMCs to a synthetic phenotype, as evidenced by an increase in VSMC proliferation, mitochondrial activity, migration, and synthesis but a decrease in VSMC apoptosis. Lactate inhibited miR-23b expression in VSMCs, and miR-23b inhibited VSMC's switch to the synthetic phenotype. Lactate modulated the VSMC phenotype through downregulation of miR-23b expression, suggesting that overexpression of miR-23b using a miR-23b mimic attenuated the effects of lactate on VSMC phenotype modulation. Moreover, we discovered that SMAD family member 3 (SMAD3) was the target of miR-23b in regulating VSMC phenotype. Further findings suggested that lactate promotes VSMC switch to synthetic phenotype by targeting SMAD3 and downregulating miR-23b. These findings suggest that correcting the dysregulation of miR-23b/SMAD3 or lactate metabolism is a potential treatment for vascular diseases.

The Essential Function of miR-5739 in Embryonic Muscle Development

  • Ji-Heon Lee;Min Sup Kim;Jin-seop Lee;Dong Hyun Lee;Chansol Park;Dong Hyuk Lee;Eun-Young Kim;Hyung Min Chung
    • International Journal of Stem Cells
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    • 제16권2호
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    • pp.145-155
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    • 2023
  • Background and Objectives: Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed. Methods and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3' untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease. Conclusions: Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regulate muscle and vascular differentiation during embryonic development.

MiR-323-5p acts as a Tumor Suppressor by Targeting the Insulin-like Growth Factor 1 Receptor in Human Glioma Cells

  • Lian, Hai-Wei;Zhou, Yun;Jian, Zhi-Hong;Liu, Ren-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권23호
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    • pp.10181-10185
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    • 2015
  • Background: MicroRNAs, small noncoding RNA molecules, can regulate mammalian cell growth, apoptosis and differentiation by controlling the expression of target genes. The aim of this study was to investigate the function of miR-323-5p in the glioma cell line, U251. Materials and Methods: After over-expression of miR-323-5p using miR-323-5p mimics, cell growth, apoptosis and migration were tested by MTT, flow cytometry and cell wound healing assay, respectively. We also assessed the influence of miR-323-5p on the mRNA expression of IGF-1R by quantitative real-time reverse transcriptase PCR (qRT-PCR), and on the protein levels by Western blot analysi. In addition, dual-luciferase reporter assays were performed to determine the target site of miR-323-5p to IGF-1R 3'UTR. Results: Our findings showed that over-expression of miR-323-5p could promote apoptosis of U251 and inhibit the proliferation and migration of the glioma cells. Conclusions: This study demonstrated that increased expression of miR-323-5p might be related to glioma progression, which indicates a potential role of miR-323-5p for clinical therapy.

다중 화면으로 구성된 차량용 헤드업 디스플레이에 대한 연구 (A Portable Head Up Display System with A Multi Windows for Vehicles)

  • 지용석
    • 방송공학회논문지
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    • 제20권6호
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    • pp.928-937
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    • 2015
  • 기존의 헤드업 디스플레이는 작은 허상 크기로 인하여 운전자가 영상 정보를 쉽게 인식할 수 없는 어려움을 가지고 있기 때문에, 본 연구에서는 수평 방향으로 영상을 넓히는 다중 화면 구조와 컴바이너 렌즈를 사용하여 영상 확대와 다채널 윈도우 구조의 헤드업 디스플레이를 연구하였다. 0.47inch 크기의 LCD를 사용하여 투과와 반사 기능의 허상 영상을 사람의 눈에서 3m 위치에 구현하는 기술을 연구하여 근거리와 원거리의 물체에 대한 운전자의 인지 시간을 짧게 하였다. 허상 영상의 콘텐츠로는 스마트 폰을 이용하여 다양한 내비게이션 정보 등을 디스플레이 할 수 있도록 하여 안전과 정보를 동시에 제공할 수 있도록 하였다.