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https://www.readbyqxmd.com/read/29748374/the-microrna-371-373-cluster-represses-colon-cancer-initiation-and-metastatic-colonization-by-inhibiting-the-tgfbr2-id1-signaling-axis
#1
Pit Ullmann, Fabien Rodriguez, Martine Schmitz, Steffen K Meurer, Komal Qureshi-Baig, Paul Felten, Aurélien Ginolhac, Laurent Antunes, Sonia Frasquilho, Nikolaus Zügel, Ralf Weiskirchen, Serge Haan, Elisabeth Letellier
The vast majority of colorectal cancer (CRC)-related deaths can be attributed to metastatic spreading of the disease. Therefore, deciphering molecular mechanisms of metastatic dissemination is a key prerequisite to improve future treatment options. With this aim, we took advantage of different CRC cell lines and recently established primary cultures enriched in colon cancer stem cells (CSCs) - also known as tumor-initiating cells (TICs) - to identify genes and microRNAs (miRNAs) with regulatory functions in CRC progression...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29721855/id1-and-sonic-hedgehog-mediate-cell-cycle-reentry-and-apoptosis-induced-by-amyloid-beta-peptide-in-post-mitotic-cortical-neurons
#2
A-Ching Chao, Chien-Hui Chen, Shih-Hsin Chang, Chao-Tzu Huang, Wei-Chao Hwang, Ding-I Yang
Amyloid beta-peptide (Aβ), the neurotoxic component of senile plaques in Alzheimer's disease (AD) brains, is known to trigger cell cycle reentry in post-mitotic neurons followed by apoptosis. However, the underlying mechanisms remain unclear. Recently, we have reported that Aβs stimulate the expression of inhibitor of differentiation-1 (Id1) to induce sonic hedgehog (SHH) (Hung et al., Mol Neurobiol 53(2):793-809, 2016), and both are mitogens capable of triggering cell cycle progression. In this work, we tested the hypothesis that Aβ-induced Id1 and SHH contribute to cell cycle reentry leading to apoptosis in neurons...
May 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29665650/selenium-nanoparticles-prevents-lead-acetate-induced-hypothyroidism-and-oxidative-damage-of-thyroid-tissues-in-male-rats-through-modulation-of-selenoenzymes-and-suppression-of-mir-224
#3
Hebatallah Husseini Atteia, Manar Hamed Arafa, Kousalya Prabahar
Selenium nanoparticles (Se-NPs) are customizable drug delivery vehicles that show good bioavailability, higher efficacy and lower toxicity than ordinary Se. Pre-treatment of male rats with these NPs has been recently shown to exert a protective effect against chromium-induced thyroid dysfunction. This study, therefore, aimed to investigate and characterize the potential protective mechanism of Se-NPs against lead (Pb) acetate-induced thyrotoxicity. We found that prophylactic and concurrent treatment of Pb acetate-exposed rats with Nano-Se (0...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29622797/novel-bone-morphogenetic-protein-receptor-inhibitor-jl5-suppresses-tumor-cell-survival-signaling-and-induces-regression-of-human-lung-cancer
#4
Jenna H Newman, David J Augeri, Rachel NeMoyer, Jyoti Malhotra, Elaine Langenfeld, Charles B Chesson, Natalie S Dobias, Michael J Lee, Saeed Tarabichi, Sachin R Jhawar, Praveen K Bommareddy, Sh'Rae Marshall, Evita T Sadimin, John E Kerrigan, Michael Goedken, Christine Minerowicz, Salma K Jabbour, Shengguo Li, Mary O Carayannopolous, Andrew Zloza, John Langenfeld
BMP receptor inhibitors induce death of cancer cells through the downregulation of antiapoptotic proteins XIAP, pTAK1, and Id1-Id3. However, the current most potent BMP receptor inhibitor, DMH2, does not downregulate BMP signaling in vivo because of metabolic instability and poor pharmacokinetics. Here we identified the site of metabolic instability of DMH2 and designed a novel BMP receptor inhibitor, JL5. We show that JL5 has a greater volume of distribution and suppresses the expression of Id1 and pTak1 in tumor xenografts...
April 6, 2018: Oncogene
https://www.readbyqxmd.com/read/29606612/heterogeneity-of-human-breast-stem-and-progenitor-cells-as-revealed-by-transcriptional-profiling
#5
Justin A Colacino, Ebrahim Azizi, Michael D Brooks, Ramdane Harouaka, Shamileh Fouladdel, Sean P McDermott, Michael Lee, David Hill, Julie Madden, Julie Boerner, Michele L Cote, Maureen A Sartor, Laura S Rozek, Max S Wicha
During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and driven by cancer stem cells characterized by CD44+ CD24low/- or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal and epithelial populations both capable of tumor initiation. Less is known about these populations in non-cancerous mammary glands. From RNA sequencing, ALDH+ and ALDH- CD44+ CD24- human mammary cells have epithelial-like and mesenchymal-like characteristics, respectively, with some co-expressing ALDH+ and CD44+ CD24- by flow cytometry...
March 20, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29508175/a-novel-role-of-id1-in-regulating-oscillatory-shear-stress-mediated-lipid-uptake-in-endothelial-cells
#6
Kang Zhang, Yidan Chen, Tian Zhang, Lu Huang, Yi Wang, Tieying Yin, Juhui Qiu, Hans Gregersen, Guixue Wang
Inhibitor of DNA binding 1 (Id1) has been shown to be involved in adipogenesis and metabolism, which may contribute to atherosclerotic progression. However, it remains unclear how Id1 regulates endothelial cell functions and atherosclerosis in response to oscillatory shear stress. The current study aims to evaluate the effects of oscillatory shear stress on LDL uptake by endothelial cells and to delineate the roles of Id1 in this process. Using an in vivo ligation model of ApoE-/- mice and applying low and oscillatory shear stress (OSS) in vitro, we found that OSS can effectively promote lipid uptake...
June 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29501651/regulation-of-brain-development-and-brain-function-by-the-transcriptional-repressor-rp58
#7
REVIEW
Haruo Okado
The mechanisms regulating the formation of the cerebral cortex have been well studied. In the developing cortex, (also known Znf238, Zfp238, and Zbtb18), which encodes a sequence-specific transcriptional repressor, is expressed in glutamatergic projection neurons and progenitor cells. Targeted deletion of Rp58 leads to dysplasia of the neocortex and hippocampus, a reduction in the number of mature cortical neurons, and defects in laminar organization due to abnormal neuronal migration within the cortical plate...
March 1, 2018: Brain Research
https://www.readbyqxmd.com/read/29464028/consecutive-epigenetically-active-agent-combinations-act-in-id1-runx3-tet2-and-hoxa-pathways-for-flt3itd-ve-aml
#8
Hamid Sayar, Yan Liu, Rui Gao, Mohammad Abu Zaid, Larry D Cripe, Jill Weisenbach, Katie J Sargent, Mehdi Nassiri, Lang Li, Heiko Konig, Attaya Suvannasankha, Feng Pan, Rajasubramaniam Shanmugam, Chirayu Goswami, Reuben Kapur, Mingjiang Xu, H Scott Boswell
Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3 , occurring along with ID1 and HOXA over-expressions...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29449428/a-novel-piperidine-identified-by-stem-cell-based-screening-attenuates-pulmonary-arterial-hypertension-by-regulating-bmp2-and-ptgs2-levels
#9
Yanjiang Xing, Shuang Zhao, Qingxia Wei, Shiqiang Gong, Xin Zhao, Fang Zhou, Rafia Ai-Lamki, Daniel Ortmann, Mingxia Du, Roger Pedersen, Guangdong Shang, Shuyi Si, Nicholas W Morrell, Jun Yang
Genetic defects in bone morphogenetic protein type II receptor (BMPRII) signalling and inflammation contribute to the pathogenesis of pulmonary arterial hypertension (PAH). The receptor is activated by bone morphogenetic protein (BMP) ligands, which also enhance BMPR2 transcription. A small-molecule BMP upregulator with selectivity on vascular endothelium would be a desirable therapeutic intervention for PAH.We assayed compounds identified in the screening of BMP2 upregulators for their ability to increase the expression of inhibitor of DNA binding 1 (Id1), using a dual reporter driven specifically in human embryonic stem cell-derived endothelial cells...
April 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29376829/tgf-%C3%AE-uses-a-novel-mode-of-receptor-activation-to-phosphorylate-smad1-5-and-induce-epithelial-to-mesenchymal-transition
#10
Anassuya Ramachandran, Pedro Vizán, Debipriya Das, Probir Chakravarty, Janis Vogt, Katherine W Rogers, Patrick Müller, Andrew P Hinck, Gopal P Sapkota, Caroline S Hill
The best characterized signaling pathway downstream of transforming growth factor β (TGF-β) is through SMAD2 and SMAD3. However, TGF-β also induces phosphorylation of SMAD1 and SMAD5, but the mechanism of this phosphorylation and its functional relevance is not known. Here, we show that TGF-β-induced SMAD1/5 phosphorylation requires members of two classes of type I receptor, TGFBR1 and ACVR1, and establish a new paradigm for receptor activation where TGFBR1 phosphorylates and activates ACVR1, which phosphorylates SMAD1/5...
January 29, 2018: ELife
https://www.readbyqxmd.com/read/29353044/bmp4-signaling-in-npcs-upregulates-bcl-xl-to-promote-their-survival-in-the-presence-of-fgf-2
#11
Hanako Yamamoto, Masashi Kurachi, Masae Naruse, Koji Shibasaki, Yasuki Ishizaki
We previously reported that BMP4 does not promote proliferation or differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In this study, we examined if BMP4 acts as a survival factor also for neural stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse brain. We found BMP4 promotes survival but not proliferation or differentiation of these cells, just as in the case for CD44-positive APCs...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29342401/matched-placental-and-circulating-plasmodium-falciparum-parasites-are-genetically-homologous-at-the-var2csa-id1-dbl2x-locus-by-deep-sequencing
#12
Andreea Waltmann, Jaymin C Patel, Kyaw L Thwai, Nicholas J Hathaway, Christian M Parobek, Achille Massougbodji, Nadine Fievet, Jeffery A Bailey, Philippe Deloron, Jonathan J Juliano, Nicaise Tuikue Ndam, Steven R Meshnick
In pregnancy-associated malaria, infected erythrocytes accumulate in the placenta. It is unclear if in polyclonal infections this results in distinct peripheral and placental parasite populations. We used long amplicon deep sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral and placental samples collected at delivery from a high transmission area to determine genetic homology. Despite substantial sequence variation and detecting 23 haplotypes, the matched pairs mostly contained the same genetic variants, with 11 pairs sharing 100% of their variants, whereas others showed some heterogeneity...
January 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29328430/vanillin-improves-scopolamine%C3%A2-induced-memory-impairment-through-restoration-of-id1-expression-in-the-mouse-hippocampus
#13
Jae-Chul Lee, In Hye Kim, Jeong Hwi Cho, Tae-Kyeong Lee, Joon Ha Park, Ji Hyeon Ahn, Bich Na Shin, Bing Chun Yan, Jong-Dai Kim, Yong Hwan Jeon, Young Joo Lee, Moo-Ho Won, Il Jun Kang
4-Hydroxy-3-methoxybenzaldehyde (vanillin), contained in a number of species of plant, has been reported to display beneficial effects against brain injuries. In the present study, the impact of vanillin on scopolamine‑induced alterations in cognition and the expression of DNA binding protein inhibitor ID‑1 (ID1), one of the inhibitors of DNA binding/differentiation proteins that regulate gene transcription, in the mouse hippocampus. Mice were treated with 1 mg/kg scopolamine with or without 40 mg/kg vanillin once daily for 4 weeks...
March 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29287202/microrna-381-suppresses-the-growth-and-increases-cisplatin-sensitivity-in-non-small-cell-lung-cancer-cells-through-inhibition-of-nuclear-factor-%C3%AE%C2%BAb-signaling
#14
Ri-Sheng Huang, Yuan-Liang Zheng, Jun Zhao, Xu Chun
microRNA (miR)-381 is downregulated and exhibits anti-invasive activity in non-small cell lung cancer (NSCLC). In this study, we investigated the role of miR-381 in proliferation, tumorigenesis, and cisplatin resistance of NSCLC cells. The effects of miR-381 overexpression on proliferation, tumorigenesis, cell cycle progression, and cisplatin sensitivity were examined. Overexpression of miR-381 significantly inhibited cell proliferation and colony formation in vitro and tumorigenesis in vivo. Ectopic expression of miR-381 arrested NSCLC cells at G0/G1 phase, which was accompanied by increased expression of p21 and p27 and decreased expression of cyclin D1 and CDK4...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29240916/study-on-the-anti-endotoxin-effect-of-sinomenine-using-an-agilent-genome-array
#15
Y Hu, B Li, L Wen, K He
Background: Endotoxin is a significant contributing factor underlying the occurrence of fever, diarrhea, inflammation, edema, coagulation, shock and other syndromes associated with gram-negative bacterial infections. To date, there is no effective treatment for endotoxemia. Aim: The aim of this study was to characterize differentially expressed genes in sinomenine-treated and lipopolysaccharide (LPS)-induced endothelial cells by microarray analysis and to determine the potential pharmacological activity of sinomenine...
March 1, 2018: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/29228234/tgfbr2-inactivation-facilitates-cellular-plasticity-and-development-of-pten-null-prostate-cancer
#16
Wei Zhao, Peng Tan, Qingyuan Zhu, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y Wang, Rong-Fu Wang
Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo...
December 8, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29223735/targeting-secreted-cytokine-bmp9-gates-the-attenuation-of-hepatic-fibrosis
#17
Peng Li, Yongyun Li, Liqi Zhu, Zhi Yang, Jie He, Lihua Wang, Qingfeng Shang, Hui Pan, Huixue Wang, Xiong Ma, Bin Li, Xianqun Fan, Shengfang Ge, Renbing Jia, He Zhang
Liver fibrosis is overly exuberant wound healing that leads to portal hypertension or liver cirrhosis. Recent studies have demonstrated the functions of bone morphogenetic protein 9 (BMP9) in liver fibrosis, and thus, targeting liver-specific BMP9 abnormalities will become an attractive approach for developing therapeutics to treat liver fibrosis. Here, we reveal that BMP9 serves as a valuable serum diagnostic indicator and efficient therapeutic target to attenuate liver fibrogenesis. Our analysis of biopsies from liver fibrotic patients revealed that higher BMP9 levels accompanied advanced stages of liver fibrosis...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29208670/inhibition-of-id1-bmpr2-intrinsic-signaling-sensitizes-glioma-stem-cells-to-differentiation-therapy
#18
Xiong Jin, Xun Jin, Leo J Y Kim, Deobrat Dixit, Hee-Young Jeon, Eun-Jung Kim, Jun-Kyum Kim, Seon Yong Lee, Jinlong Yin, Jeremy N Rich, Hyunggee Kim
Purpose: Normal stem cells tightly control self-renewal and differentiation during development, but their neoplastic counterparts, cancer stem cells (CSCs), sustain tumorigenicity both through aberrant activation of stemness and evasion of differentiation. Although regulation of CSC stemness has been extensively studied, the molecular mechanisms suppressing differentiation remain unclear. Experimental Design: We performed in silico screening and in vitro validation studies through Western blotting, qRT-PCR for treatment of WNT and SHH signaling inhibitors, and BMP signaling inducer with control and ID1-overexpressing cells...
January 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29207147/effect-and-mechanism-of-rnai-targeting-wwtr1-on-biological-activity-of-gastric-cancer-cells-sgc7901
#19
Yuan Li, Fang-Liang Yang, Chun-Fu Zhu, Li-Ming Tang
Gastric cancer (GC) is one of the most common malignancies in the world. It is essential to develop novel targets and therapeutic approaches for GC, which requires identification of novel functional molecules. WW‑domain containing transcription regulator 1 (WWTR1) may activate many transcriptional factors and exhibit an important role in the development of various tissues in mammals. The results of the present study demonstrated that mRNA and protein levels of WWTR1 are increased in GC tissues and cell lines...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29203239/piperine-induces-osteoblast-differentiation-through-ampk-dependent-runx2-expression
#20
Do-Young Kim, Eun-Jung Kim, Won-Gu Jang
Piperine is an alkaloid responsible for the pungency of black pepper and long pepper. It is reported to have various biological actions such as anti-oxidative and anti-inflammatory, and aids cancer prevention. Antioxidants have been shown to promote osteoblast differentiation. However, osteoblast differentiation by piperine has not yet been elucidated. Piperine-induced expression of the osteogenic genes such as distal-less homeobox 5 (Dlx5), inhibitor of DNA binding-1 (Id1), and runt-related transcription factor 2 (Runx2) was investigated using RT-PCR...
January 1, 2018: Biochemical and Biophysical Research Communications
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