miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Kim, Youngmi,Kim, Hyuna,Park, Hyunmi,Park, Deokbum,Lee, Hansoo,Lee, Yun Sil,Choe, Jongseon,Kim, Young Myeong,Jeoung, Dooil American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.40

<P>Histone modification is known to be associated with multidrug resistance phenotypes. Cancer cell lines that are resistant or have been made resistant to anti-cancer drugs showed lower expression levels of histone deacetylase-3 (HDAC3), among the histone deacetylase(s), than cancer cell lines that were sensitive to anti-cancer drugs. Celastrol and Taxol decreased the expression of HDAC3 in cancer cell lines sensitive to anti-cancer drugs. HDAC3 negatively regulated the invasion, migration, and anchorage-independent growth of cancer cells. HDAC3 conferred sensitivity to anti-cancer drugs <I>in vitro</I> and <I>in vivo</I>. TargetScan analysis predicted <I>miR-326</I> as a negative regulator of HDAC3. ChIP assays and luciferase assays showed a negative feedback loop between HDAC3 and <I>miR-326. miR-326</I> decreased the apoptotic effect of anti-cancer drugs, and the <I>miR-326</I> inhibitor increased the apoptotic effect of anti-cancer drugs. <I>miR-326</I> enhanced the invasion and migration potential of cancer cells. The <I>miR-326</I> inhibitor negatively regulated the tumorigenic, metastatic, and angiogenic potential of anti-cancer drug-resistant cancer cells. HDAC3 showed a positive feedback loop with miRNAs such as <I>miR-200b</I>, <I>miR-217</I>, and <I>miR-335. miR-200b</I>, <I>miR-217</I>, and <I>miR-335</I> negatively regulated the expression of <I>miR-326</I> and the invasion and migration potential of cancer cells while enhancing the apoptotic effect of anti-cancer drugs. TargetScan analysis predicted <I>miR-200b</I> and <I>miR-217</I> as negative regulators of cancer-associated gene, a cancer/testis antigen, which is known to regulate the response to anti-cancer drugs. HDAC3 and <I>miR-326</I> acted upstream of the cancer-associated gene. Thus, we show that the miR-326-HDAC3 feedback loop can be employed as a target for the development of anti-cancer therapeutics.</P>

Transglutaminase II interacts with rac1, regulates production of reactive oxygen species, expression of snail, secretion of Th2 cytokines and mediates <i>in vitro</i> and <i>in vivo</i> allergic inflammation

Kim, Youngmi,Eom, Sangkyung,Kim, Kyungjong,Lee, Yun-Sil,Choe, Jongseon,Hahn, Jang Hee,Lee, Hansoo,Kim, Young-Myeong,Ha, Kwon Soo,Ro, Jai Youl,Jeoung, Dooil Elsevier 2010 Molecular immunology Vol.47 No.5

<P><B>Abstract</B></P><P>Transglutaminase II (TGase II) is a protein cross-linking enzyme with diverse biological functions. Here we report the role of TGase II in allergic inflammation. Antigen stimulation induced expression and activity of TGase II by activation of NF-κB in rat basophilic leukemia (RBL2H3) cells. This induction of TGase II was dependent on FcϵRI and EGFR. Interaction between TGase II and rac1 was induced following antigen stimulation. TGase II was responsible for the increased production of reactive oxygen species, expression of prostaglandin E2 synthase (PGE2 synthase) and was responsible for increased secretion of prostaglandin E2. ChIP assay showed that TGase II, through interaction with NF-κB, was responsible for the induction of histone deacetylase-3 (HDAC3) and snail by direct binding to promoter sequences. HDAC3 and snail induced by TGase II, exerted transcriptional repression on E-cadherin. Snail exerted negative effect on expression of MMP-2, and secretion of Th2 cytokines. Inhibition of matrix metalloproteinase-2 (MMP-2) inhibited secretion of Th2 cytokines. <I>In vivo</I> induction of TGase II was observed in Balb/c mouse model of IgE antibody-induced passive cutaneous anaphylaxis. Chemical inhibition of TGase II exerted negative effect on IgE-dependent passive cutaneous anaphylaxis. Chemical inhibition of TGase II by cystamine exerted negative effect on Balb/c mouse model of phorbol myristate acetate (PMA)-induced atopic dermatitis. These results suggest novel role of TGase II in allergic inflammation and TGase II can be developed as target for the development of allergy therapeutics.</P>

miR-200b and Cancer/Testis Antigen CAGE Form a Feedback Loop to Regulate the Invasion and Tumorigenic and Angiogenic Responses of a Cancer Cell Line to Microtubule-targeting Drugs

Kim, Youngmi,Park, Deokbum,Kim, Hyuna,Choi, Munseon,Lee, Hansoo,Lee, Yun Sil,Choe, Jongseon,Kim, Young Myeong,Jeoung, Dooil American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.51

<P>Cancer/testis antigen <U>ca</U>ncer-associated <U>ge</U>ne (CAGE) is known to be involved in various cellular processes, such as proliferation, cell motility, and anti-cancer drug resistance. However, the mechanism of the expression regulation of CAGE remains unknown. Target scan analysis predicted the binding of microRNA-200b (miR-200b) to CAGE promoter sequences. The expression of CAGE showed an inverse relationship with miR-200b in various cancer cell lines. miR-200b was shown to bind to the 3′-UTR of CAGE and to regulate the expression of CAGE at the transcriptional level. miR-200b also enhanced the sensitivities to microtubule-targeting drugs <I>in vitro</I>. miR-200b and CAGE showed opposite regulations on invasion potential and responses to microtubule-targeting drugs. Xenograft experiments showed that miR-200b had negative effects on the tumorigenic and metastatic potential of cancer cells. The effect of miR-200b on metastatic potential involved the expression regulation of CAGE by miR-200b. miR-200b decreased the tumorigenic potential of a cancer cell line resistant to microtubule-targeting drugs in a manner associated with the down-regulation of CAGE. ChIP assays showed the direct regulation of miR-200b by CAGE. CAGE enhanced the invasion potential of a cancer cell line stably expressing miR-200b. miR-200b exerted a negative regulation on tumor-induced angiogenesis. The down-regulation of CAGE led to the decreased expression of plasminogen activator inhibitor-1, a TGFβ-responsive protein involved in angiogenesis, and VEGF. CAGE mediated tumor-induced angiogenesis and was necessary for VEGF-promoted angiogenesis. Human recombinant CAGE protein displayed angiogenic potential. Thus, miR-200b and CAGE form a feedback regulatory loop and regulate the response to microtubule-targeting drugs, as well as the invasion, tumorigenic potential, and angiogenic potential.</P>

Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis

Kim, Min-Seon,Pak, Youngmi K,Jang, Pil-Geum,Namkoong, Cherl,Choi, Yon-Sik,Won, Jong-Chul,Kim, Kyung-Sup,Kim, Seung-Whan,Kim, Hyo-Soo,Park, Joong-Yeol,Kim, Young-Bum,Lee, Ki-Up Nature Publishing Group 2006 NATURE NEUROSCIENCE Vol.9 No.7

Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest that the forkhead transcription factor Foxo1 is an important mediator of insulin signaling in peripheral tissues. Here we demonstrate that in normal mice, hypothalamic Foxo1 expression is reduced by the anorexigenic hormones insulin and leptin. These hormones' effects on feeding are inhibited when hypothalamic Foxo1 is activated, establishing a new signaling pathway through which insulin and leptin regulate food intake in hypothalamic neurons. Moreover, activation of Foxo1 in the hypothalamus increases food intake and body weight, whereas inhibition of Foxo1 decreases both. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, but suppresses the transcription of anorexigenic proopiomelanocortin by antagonizing the activity of signal transducer–activated transcript-3 (STAT3). Our data suggest that hypothalamic Foxo1 is an important regulator of food intake and energy balance.

Celastrol binds to ERK and inhibits FcεRI signaling to exert an anti-allergic effect

Kim, Youngmi,Kim, Kyungjong,Lee, Hansoo,Han, Sanghwa,Lee, Yun-Sil,Choe, Jongseon,Kim, Young-Myeong,Hahn, Jang-Hee,Ro, Jai Youl,Jeoung, Dooil Elsevier 2009 european journal of pharmacology Vol.612 No.1

<P><B>Abstract</B></P><P>The role of celastrol, a triterpene extracted from the Chinese “Thunder of God Vine,” in allergic inflammation was investigated. Celastrol decreased the secretion of β-hexosaminidase, decreased the release of histamine, decreased the expression of Th2 cytokines and decreased calcium influx and cell adhesion in antigen-stimulated RBL2H3 cells. Exposure to celastrol decreased the phosphorylation of extracellular regulated kinase (ERK) and the ERK kinase activity was decreased in RBL2H3 cells. A molecular dynamics simulation showed binding of celastrol to a large pocket in ERK2, which serves as the ATP-binding site. Exposure to celastrol inhibited the interaction between immunoglobulin Fc epsilon receptor I (FcεRIγ) and ERK and inhibited interaction between FcεRIγ and protein kinase C δ (PKCδ). Antigen stimulation induced an interaction between Rac1 and ERK as well as an interaction between Rac1 and PKCδ. Inhibition of ERK decreased Rac1 activity and inhibition of Rac1 decreased ERK activity in antigen-stimulated RBL2H3 cells. Celastrol regulated the expression of epithelial–mesenchymal transition (EMT)-related proteins through inhibition of PKCα, PKCδ, and Rac1 in antigen-stimulated RBL2H3 cells. Exposure to celatrol inhibited PKCδ activity in antigen-stimulated RBL2H3 cells. Celastrol exerted a negative effect on FcεRIβ signaling by inhibiting the interaction between heat shock protein 90 (hsp90) and proteins, such as, FcεRIβ, Akt and PKCα. Celastrol exerted a negative effect on <I>in vivo</I> atopic dermatitis induced by 2, 4-dinitrofluorobenzene (DNFB), which requires ERK. Celastrol also showed an inhibitory effect on skin inflammation induced by phorbol myristate acetate (PMA) in Balb/c mice. In summary, celastrol binds to ERK and inhibits FcεRI signaling to exert an anti-inflammatory effect.</P>

Evaluation of Antigen-Specific Immunoglobulin G Responses in Pulmonary Tuberculosis Patients and Contacts

Hur, Yun-Gyoung,Kim, Ahreum,Kang, Young Ae,Kim, An Sik,Kim, Dae Yeon,Kim, Yeun,Kim, Youngmi,Lee, Hyeyoung,Cho, Sang-Nae American Society for Microbiology 2015 Journal of clinical microbiology Vol.53 No.3

<P>This study aimed to evaluate the serodiagnostic potential of immunoglobulin G (IgG) responses to <I>Mycobacterium tuberculosis</I> antigens in pulmonary tuberculosis (TB) patients, recent TB contacts with latent TB infection (LTBI), and healthy subjects. Infections were assessed using tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, drug susceptibility testing, and molecular genotyping of clinical isolates. Serum IgG responses to selective <I>M. tuberculosis</I> antigens, including the 38-kDa and 16-kDa antigens, lipoarabinomannan (LAM), and recombinant early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10), were determined. We found that the serum IgG responses to all antigens might differentiate between active TB and LTBI, with LAM having the highest diagnostic value (area under the curve [AUC] of 0.7756, <I>P</I> < 0.001). Recurrent TB cases showed significantly higher IgG responses to 38 kDa, CFP-10 (<I>P</I> < 0.01), and LAM (<I>P</I> < 0.05) than new cases, and male patients had higher levels of antigen-specific IgG than females (<I>P</I> < 0.05). Conversely, drug resistance and patient body mass index did not affect IgG responses (<I>P</I> > 0.05). LAM-specific IgG responses differentiated between acid-fast bacillus (AFB) smear-positive and -negative patients (<I>P</I> < 0.01), whereas antigen-specific IgG responses did not vary with the <I>M. tuberculosis</I> genotype (<I>P</I> > 0.05). Significantly higher IgG responses to 38 kDa and 16 kDa were observed in AFB smear-negative patients than in controls. These results suggest that assessment of serum IgG responses to selective purified <I>M. tuberculosis</I> antigens may help improve the diagnosis of active TB, particularly for sputum smear-negative patients or recurrent cases, and these may also help to differentiate between active TB and LTBI.</P>

Synthesis and catalytic activity of electrospun NiO/NiCo₂O₄ nanotubes for CO and acetaldehyde oxidation

Kim, Il Hee,Lee, Hyerim,Yu, Areum,Jeong, Jae Hwan,Lee, Youngmi,Kim, Myung Hwa,Lee, Chongmok,Kim, Young Dok IOP 2018 Nanotechnology Vol.29 No.17

<P>NiO/NiCo<SUB>2</SUB>O<SUB>4</SUB> nanotubes with a diameter of approximately 100 nm are synthesized using Ni and Co precursors via electro-spinning and subsequent calcination processes. The tubular structure is confirmed via transmission electron microscopy imaging, whereas the structures and elemental compositions of the nanotubes are determined using x-ray diffraction, energy dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. N<SUB>2</SUB> adsorption isotherm data reveal that the surface of the nanotubes consists of micropores, thereby resulting in a significantly higher surface area (∼20 m<SUP>2</SUP> g<SUP>−1</SUP>) than expected for a flat-surface structure (<15 m<SUP>2</SUP> g<SUP>−1</SUP>). Herein, we present a study of the catalytic activity of our novel NiO/NiCo<SUB>2</SUB>O<SUB>4</SUB> nanotubes for CO and acetaldehyde oxidation. The catalytic activity of NiO/NiCo<SUB>2</SUB>O<SUB>4</SUB> is superior to Pt below 100 °C for CO oxidation. For acetaldehyde oxidation, the total oxidation activity of NiO/NiCo<SUB>2</SUB>O<SUB>4</SUB> for acetaldehyde is comparable with that of Pt. Coexistence of many under-coordinated Co and Ni active sites in our structure is suggested be related to the high catalytic activity. It is suggested that our novel NiO/NiCo<SUB>2</SUB>O<SUB>4</SUB> tubular structures with surface microporosity can be of interest for a variety of applications, including the catalytic oxidation of harmful gases.</P>

A Water Indicator Strip: Instantaneous Fluorogenic Detection of Water in Organic Solvents, Drugs, and Foodstuffs

Kim, Tae-Il,Kim, Youngmi American Chemical Society 2017 ANALYTICAL CHEMISTRY - Vol.89 No.6

<P>A simple, highly sensitive, and rapid colorimetric and fluorescent indicator 1 has been developed for the qualitative and quantitative determination of water. The water induced sensitive (LOD = 0.003%, v/v) and fast (<10 s) change in emission properties was applied to the determination of water in organic solvents, drugs, and foodstuffs in both solution and practical solid-state indicator paper strips.</P>

DECOMPOSITIONS AND EXPANSIONS OF FILTERS IN TARSKI ALGEBRAS

Kim, Jaedeok,Kim, Youngmi,Roh, Eun Hwan 충청수학회 2007 충청수학회지 Vol.20 No.4

We show that any filter of Tarski algebra can be de-composed into the union of some sets. Moreover, we introduce the notion of expansions of filters in Tarski algebras, and discuss the notion of ${\sigma}$-primary filters in Tarski algebras. Finally, we show that there is no non-trivial quadratic Tarski algebras on a field X with $|X|{\geq}3$.

Evolution of silver to a better electrocatalyst: Water-assisted oxygen reduction reaction at silver chloride nanowires in alkaline solution

Kim, Su-jin,Lee, Seung-Cheol,Lee, Chongmok,Kim, Myung Hwa,Lee, Youngmi Elsevier 2018 Nano energy Vol.48 No.-

<P><B>Abstract</B></P> <P>Oxygen reduction reaction (ORR) is of great interest in various areas, including energy conversion. This paper presents the simple synthesis and characterization of one-dimensional silver halides nanowires (AgClNW and AgBrNW) as an electrocatalyst for ORR in alkaline media, as well as an investigation of the ORR pathway at AgCl. AgClNW and AgBrNW were prepared via a galvanic replacement reaction (GRR) between silver nanowires (AgNW) and a halide precursor. AgClNW exhibited excellent ORR catalytic activity that was comparable to or better than that for commercial Pt (20 wt% Pt loading on Vulcan carbon), demonstrating potential to replace Pt-based catalysts. A scanning electrochemical microscopy (SECM) analysis supports the existence of an associative ORR pathway at AgCl, and first-principles density functional theory (DFT) calculations suggest that the high ORR activity of AgCl is possibly attributed to the up-shifted Ag d-band center energy in AgCl as well as the assistance of adsorbed water molecules.</P> <P><B>Highlights</B></P> <P> <UL> <LI> AgCl nanowires show an excellent catalytic activity for oxygen reduction reaction. </LI> <LI> AgCl nanowires are synthesized from Ag nanowires via galvanic replacement reaction. </LI> <LI> d-band center energy of Ag in AgCl is upshifted to become closer to that of Pt. </LI> <LI> Water adsorption on AgCl plays a critical role in the improved activity of AgCl. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Silver chloride nanowires show an excellent electrocatalytic activity for oxygen reduction reaction via water assistance.</P> <P>[DISPLAY OMISSION]</P>