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BMB Reports

Hyuk Moon, Kwang-Hyub Han, Simon Weonsang Ro
Many studies have focused on the tumor suppressive role of TGF-β signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of TGF-β inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, TGF-β inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical TGF-β signaling in tumorigenesis...
October 25, 2017: BMB Reports
Hyunsung Park
Hypoxia affects various physiological and pathophyological processes. Hypoxia changes the expression of the hypoxia-responsive genes through two main pathways. First, hypoxia activates transcription factors (TF) such as Hypoxia-inducible Factor (HIF). Second, hypoxia decreases the activity of Jumonji C domain-containing histone demethylases (JMJDs) that require O2 and α-Ketoglutarate (α-KG) as substrates. The JMJDs affect gene expression through their regulation of the active or repressive histone methylations...
October 25, 2017: BMB Reports
Seung-Ju Yang, Jiae Kim, Sang Eun Lee, Jee-Yin Ahn, Soo Young Choi, Sung-Woo Cho
We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid β (Aβ)-treated primary microglial cells. KHG26792 attenuated the Aβ-induced production of inflammatory mediators such as IL-6, IL-1β, TNF-α, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by Aβ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the Aβ-induced increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of Akt/GSK-3β signaling and by decreasing the Aβ-induced translocation of NF-κB...
October 25, 2017: BMB Reports
A Rome Paek, Ji Young Mun, Kyeong-Man Hong, Jongkeun Lee, Dong Wan Hong, Hye Jin You
We previously reported the involvement of zinc-finger protein 143(ZNF143) on cancer cell motility in colon cancer cells. Here, ZNF143 was further characterized in breast cancer. Immunohistochemistry was used to determine the expression of ZNF143 in normal tissues and in tissues from metastatic breast cancer at various stages. Notably, ZNF143 was selectively expressed in duct and gland epithelium of normal breast tissues, which decreased when the tissue became malignant. To determine the molecular mechanism how ZNF143 affects breast cancer progression, it was knocked down by infecting benign breast cancer cells with short-hairpin(sh) RNA-lentiviral particles against ZNF143(MCF7 sh-ZNF143)...
October 25, 2017: BMB Reports
Nayoung Suh, Eun-Bi Lee
In most clinical applications, human mesenchymal stem cells (hMSCs) are expanded in large scale before their administration. Prolonged culture in vitro results in cellular senescence-associated phenotypes, including accumulation of reactive oxygen species (ROS) and decreased cell viabilities. Profiling of stem cell-related genes during in vitro expansion revealed that numerous canonical pathways were significantly changed. To determine the effect of selenocysteine (Sec), a rare amino acid found in several antioxidant enzymes, on the replicative senescence in hMSCs, we treated senescent hMSCs with Sec...
October 25, 2017: BMB Reports
Young-Chang Cho, Ba Reum Kim, Sayeon Cho
Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-α, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-α. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression...
October 25, 2017: BMB Reports
Seong Jeong Park, Ji-Hae Kim, Mi-Young Song, Young Chul Sung, Seung-Woo Lee, Yunji Park
Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 (PD-1-/-) did not develop colon inflammation. Interestingly, PD-1-/- mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of PD-1-/- mice to colitis is dependent on their gut microbiota...
October 25, 2017: BMB Reports
Hyun-Joo Park, Mi-Kyoung Kim, Yeon Kim, Sun Sik Bae, Hyung Joon Kim, Soo-Kyung Bae, Moon-Kyoung Bae
Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs...
October 25, 2017: BMB Reports
Won Kyu Kim, Yujin Kwon, Minhee Park, Seongju Yun, Ja-Young Kwon, Hoguen Kim
High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its dysregulated expression correlates with inflammatory diseases, ischemia, and cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis. Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown. In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed...
October 25, 2017: BMB Reports
Doyeon Kim, Hee Ryung Chang, Daehyun Baek
MicroRNAs (miRNAs) are ~22nt-long single-stranded RNA molecules that form a RNA-induced silencing complex with Argonaute (AGO) protein to post-transcriptionally downregulate their target messenger RNAs (mRNAs). To understand the regulatory mechanisms of miRNA, discovering the underlying functional rules for how miRNAs recognize and repress their target mRNAs is of utmost importance. To determine functional miRNA targeting rules, previous studies extensively utilized various methods including high-throughput biochemical assays and bioinformatics analyses...
September 26, 2017: BMB Reports
Sang Eun Jung, Kyoung-Jin Shin, Hwan Young Lee
Aging is a natural and gradual process in human life. It is influenced by heredity, environment, lifestyle, and disease. DNA methylation varies with age, and the ability to predict the age of donor using DNA from evidence materials at a crime scene is of considerable value in forensic investigations. Recently, many studies have reported age prediction models based on DNA methylation from various tissues and body fluids. Those models seem to be very promising because of their high prediction accuracies. In this review, the changes of age-associated DNA methylation and the age prediction models for various tissues and body fluids were examined, and then the applicability of the DNA methylation-based age prediction method to the forensic investigations was discussed...
September 26, 2017: BMB Reports
Do-Hyoung Kim, Anthony Wright, Kyou-Hoon Han
A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ∼70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which might be important for its activity...
October 2017: BMB Reports
Hyun-Jung Choi, Seung-Sik Rho, Dong-Hoon Choi, Young-Guen Kwon
Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish...
September 26, 2017: BMB Reports
Sang-Su Kim, Cheol Hong Kim, Ji Wook Kim, Hsi Chiang Kung, Tae Woo Park, Yu Som Shin, Ju Deok Kim, Siejeong Ryu, Wang-Joon Kim, Yung Hyun Choi, Kyoung Seob Song
CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While the overexpression of claudin-1 decreased CLB2.0-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetylcysteine inhibited CLB2...
October 2017: BMB Reports
Young-Ho Park, Hyun-Sun Kim, Jong-Hee Lee, Seon-A Choi, Jin-Man Kim, Goo Taeg Oh, Sang Won Kang, Sun-Uk Kim, Dae-Yeul Yu
Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16INK4a expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I-/- MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I-/- mice showed an increased number of cells with senescence associated-β-galactosidase (SA-β-gal) activity in a variety of tissues...
October 2017: BMB Reports
Dahye Jang, Yu Mi Baek, Hanna Park, Yeo Eun Hwang, Dong-Eun Kim
Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions...
September 12, 2017: BMB Reports
Michael Ebeid, Sung-Ho Huh
Mammalian inner ear comprises of six sensory organs; cochlea, utricle, saccule, and three semicircular canals. The cochlea contains sensory epithelium known as the organ of Corti which senses sound through mechanosensory hair cells. Mammalian inner ear undergoes series of morphogenesis during development by beginning thickening of ectoderm nearby hindbrain. These events require tight regulation of multiple signaling cascades including FGF, Wnt, Notch and Bmp signaling. In this review, we will discuss the role of newly emerging signaling, FGF signaling, for its roles required for cochlear development...
August 31, 2017: BMB Reports
Daeun You, Seung Pil Jung, Yisun Jeong, Soo Youn Bae, Jeong Eon Lee, Sangmin Kim
Fibronectin (FN) plays important roles in the EMT in a variety of cancer cell types. However, the mechanism by which FN expression is regulated in tamoxifen-resistant (TamR) breast cancer cells has not yet been fully elucidated. Aberrant FN expression was associated with poor prognosis in patients with luminal type A breast cancer. In addition, FN was upregulated in TamR cells. To investigate the mechanism by which FN expression is regulated, we assessed the levels of phosphorylated Akt, JNK, and STAT3 and found that they were all increased in TamR cells...
August 31, 2017: BMB Reports
Chan-Gi Pack, Yuji Inoue, Takashi Higurashi, Shigeko Kawai-Noma, Daigo Hayashi, Elizabeth Craig, Hideki Taguchi
Budding yeast has dozens of prions, which are mutually dependent on each other for the de novo prion formation. In addition to the interactions among prions, transmissions of prions are strictly dependent on two chaperone systems: the Hsp104 and the Hsp70/Hsp40 (J-protein) systems, both of which cooperatively remodel the prion aggregates to ensure the multiplication of prion entities. Since it has been postulated that prions and the remodeling factors constitute complex networks in cells, a quantitative approach to describe the interactions in live cells would be required...
September 2017: BMB Reports
Eunkyeong Jang, Hye Rim Lee, Geon Hee Lee, Ah-Reum Oh, Ji-Young Cha, Kazuhiko Igarashi, Jeehee Youn
The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed CD4+ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect...
September 2017: BMB Reports
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