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https://www.readbyqxmd.com/read/28222438/microrna-29b-inhibits-angiogenesis-by-targeting-vegfa-through-the-mapk-erk-and-pi3k-akt-signaling-pathways-in-endometrial-carcinoma
#1
Hong-Xia Chen, Xiao-Xia Xu, Bu-Zhen Tan, Zhi Zhang, Xiao-Dong Zhou
OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway)...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28220790/in-vivo-genome-editing-with-a-small-cas9-orthologue-derived-from-campylobacter-jejuni
#2
Eunji Kim, Taeyoung Koo, Sung Wook Park, Daesik Kim, Kyoungmi Kim, Hee-Yeon Cho, Dong Woo Song, Kyu Jun Lee, Min Hee Jung, Seokjoong Kim, Jin Hyoung Kim, Jeong Hun Kim, Jin-Soo Kim
Several CRISPR-Cas9 orthologues have been used for genome editing. Here, we present the smallest Cas9 orthologue characterized to date, derived from Campylobacter jejuni (CjCas9), for efficient genome editing in vivo. After determining protospacer-adjacent motif (PAM) sequences and optimizing single-guide RNA (sgRNA) length, we package the CjCas9 gene, its sgRNA sequence, and a marker gene in an all-in-one adeno-associated virus (AAV) vector and produce the resulting virus at a high titer. CjCas9 is highly specific, cleaving only a limited number of sites in the human or mouse genome...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28209587/genome-surgery-using-cas9-ribonucleoproteins-for-the-treatment-of-age-related-macular-degeneration
#3
Kyoungmi Kim, Sung Wook Park, Jin Hyoung Kim, Seung Hwan Lee, Daesik Kim, Taeyoung Koo, Kwang-Eun Kim, Jeong Hun Kim, Jin-Soo Kim
RNA-guided genome surgery using CRISPR-Cas9 nucleases has shown promise for the treatment of diverse genetic diseases. Yet, the potential of such nucleases for therapeutic applications in nongenetic diseases is largely unexplored. Here, we focus on age-related macular degeneration (AMD), a leading cause of blindness in adults, which is associated with retinal overexpression of, rather than mutations in, the VEGFA gene. Subretinal injection of preassembled, Vegfa gene-specific Cas9 ribonucleoproteins (RNPs) into the adult mouse eye gave rise to mutagenesis at the target site in the retinal pigment epithelium...
February 16, 2017: Genome Research
https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#4
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
February 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28202289/rolipram-potentiates-bevacizumab-induced-cell-death-in-human-glioblastoma-stem-like-cells
#5
Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Mahmoudreza Hadjighasem, Parisa Hayat, Naser Amini, Mohammad Taghi Joghataei
AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system...
February 12, 2017: Life Sciences
https://www.readbyqxmd.com/read/28199833/fgf21-administration-suppresses-retinal-and-choroidal-neovascularization-in-mice
#6
Zhongjie Fu, Yan Gong, Raffael Liegl, Zhongxiao Wang, Chi-Hsiu Liu, Steven S Meng, Samuel B Burnim, Nicholas J Saba, Thomas W Fredrick, Peyton C Morss, Ann Hellstrom, Saswata Talukdar, Lois E H Smith
Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28197812/mcpip1-contributes-to-clear-cell-renal-cell-carcinomas-development
#7
Janusz Ligeza, Paulina Marona, Natalia Gach, Barbara Lipert, Katarzyna Miekus, Waclaw Wilk, Janusz Jaszczynski, Andrzej Stelmach, Agnieszka Loboda, Jozef Dulak, Wojciech Branicki, Janusz Rys, Jolanta Jura
Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues...
February 14, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28192065/vascular-endothelial-growth-factor-a-and-leptin-expression-associated-with-ectopic-proliferation-and-retinal-dysplasia-in-zebrafish-optic-pathway-tumors
#8
Laura E Schultz, Staci L Solin, Wesley A Wierson, Janna M Lovan, Judith Syrkin-Nikolau, Deborah E Lincow, Andrew J Severin, Donald S Sakaguchi, Maura McGrail
In the central nervous system injury induces cellular reprogramming and progenitor proliferation, but the molecular mechanisms that limit regeneration and prevent tumorigenesis are not completely understood. We previously described a zebrafish optic pathway tumor model in which transgenic Tg(flk1:RFP)is18/+ adults develop nonmalignant retinal tumors. Key pathways driving injury-induced glial reprogramming and regeneration contributed to tumor formation. In this study, we examine a time course of proliferation and present new analyses of the Tg(flk1:RFP)is18/+ dysplastic retina and tumor transcriptomes...
February 13, 2017: Zebrafish
https://www.readbyqxmd.com/read/28181149/genome-wide-sequencing-reveals-micrornas-downregulated-in-cerebral-cavernous-malformations
#9
Souvik Kar, Kiran Kumar Bali, Arpita Baisantry, Robert Geffers, Amir Samii, Helmut Bertalanffy
Cerebral cavernous malformations (CCM) are vascular lesions associated with loss-of-function mutations in one of the three genes encoding KRIT1 (CCM1), CCM2, and PDCD10. Recent understanding of the molecular mechanisms that lead to CCM development is limited. The role of microRNAs (miRNAs) has been demonstrated in vascular pathologies resulting in loss of tight junction proteins, increased vascular permeability and endothelial cell dysfunction. Since the relevance of miRNAs in CCM pathophysiology has not been elucidated, the primary aim of the study was to identify the miRNA-mRNA expression network associated with CCM...
February 8, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28179359/vegfa-activates-an-epigenetic-pathway-upregulating-ovarian-cancer-initiating-cells
#10
Kibeom Jang, Minsoon Kim, Candace A Gilbert, Fiona Simpkins, Tan A Ince, Joyce M Slingerland
The angiogenic factor, VEGFA, is a therapeutic target in ovarian cancer (OVCA). VEGFA can also stimulate stem-like cells in certain cancers, but mechanisms thereof are poorly understood. Here, we show that VEGFA mediates stem cell actions in primary human OVCA culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. The VEGFA-mediated increase in spheres was abrogated by Src inhibition or SRC knockdown. VEGFA stimulated sphere formation only in the ALDH1(+) subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1...
February 8, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28179297/cilengitide-and-cetuximab-reduce-cytokine-production-and-colony-formation-of-head-and-neck-squamous-cell-carcinoma-cells-ex-vivo
#11
Gunnar Wichmann, Susan Cedra, Daphne Schlegel, Marlen Kolb, Susanne Wiegand, Andreas Boehm, Mathias Hofer, Andreas Dietz
BACKGROUND/AIM: To analyze ex vivo effects of combined targeting of the epidermal growth factor-receptor (EGFR) by cetuximab (E) plus αVβ3 and αVβ5 integrins by cilengitide (Cil) on colony formation of epithelial cells (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines in head and neck squamous cell carcinoma (HNSCC) cells. MATERIALS AND METHODS: Collagenase-IV digests of 43 histopathological confirmed HNSCC cases were seeded into laminin-coated 96-well plates containing E, Cil, or Cil+E in final concentrations of 66...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28178662/association-between-single-nucleotide-variants-of-vascular-endothelial-growth-factor-a-and-the-risk-of-thyroid-carcinoma-and-nodular-goiter-in-a-han-chinese-population
#12
Rui Liu, Lifeng Ning, Xiaoli Liu, Huiping Zhang, Yaqin Yu, Shangchao Zhang, Wenwang Rao, Jieping Shi, Hui Sun, Qiong Yu
The aim of the present study was to investigate whether genetic variants in the vascular endothelial growth factor A gene (VEGFA) were risk factors for papillary thyroid carcinoma (PTC) or nodular goiter (NG) in Han Chinese. A total of 2,319 subjects (861 PTC patients, 562 NG patients, and 896 healthy controls) were included. Five tag single nucleotide polymorphisms (tagSNPs: rs3024997, rs3025040, rs833070, rs25648, and rs10434) in VEGFA were genotyped. SNP rs3025040 T allele was associated with a decreased risk of NG (P<0...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177701/acute-upregulation-of-pgc-1%C3%AE-mrna-correlates-with-training-induced-increases-in-sdh-activity-in-human-skeletal-muscle
#13
Jacob T Bonafiglia, Brittany A Edgett, Brittany L Baechler, Matthew William Nelms, Craig A Simpson, Joe Quadrilatero, Brendon J Gurd
The purpose of the present study was to determine if acute responses in pgc-1α, vegfa, sdha, and gpd1/2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH/GPD activity and substrate storage) and morphological (fibre type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from fourteen recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 hours after (3HR) the completion of an acute bout of SIT (eight, 20-second intervals at ~170% VO2peak work rate separated by 10 seconds of recovery)...
February 2, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28165144/kaposi-s-sarcoma-associated-herpesvirus-kshv-encoded-micrornas-promote-matrix-metalloproteinases-mmps-expression-and-pro-angiogenic-cytokine-secretion-in-endothelial-cells
#14
Yuanyuan Guo, Wan Li, Jie Qin, Chun Lu, Weifei Fan
The human oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to Kaposi's sarcoma (KS), a tumor of endothelial cells characterized by angiogenesis and invasiveness. KSHV genome encodes 25 mature microRNAs (miRNAs), but their roles in KSHV-induced tumor dissemination and angiogenesis are not fully understood. In this study, we constructed the sensor reporters of KSHV miRNAs and used a luciferase reporter assay to demonstrate the function of the mimics of KSHV miRNAs. Then, we examined the expression of matrix metalloproteinases (MMPs) and pro-angiogenic cytokines that are related to cell migration and angiogenesis in the KSHV 25 miRNAs transfected endothelial cells...
February 6, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28163656/global-expression-profile-of-tumor-stem-like-cells-isolated-from-mmq-rat-prolactinoma-cell
#15
Zhipeng Su, Lin Cai, Jianglong Lu, Chuzhong Li, Songbai Gui, Chunhui Liu, Chengde Wang, Qun Li, Qichuan Zhuge, Yazhuo Zhang
BACKGROUND: Cancer stem cells (CSCs), which have been isolated from various malignancies, were closely correlated with the occurrence, progression, metastasis and recurrence of the malignant cancer. Little is known about the tumor stem-like cells (TSLCs) isolated from benign tumors. Here we want to explore the global expression profile of RNA of tumor stem-like cells isolated from MMQ rat prolactinoma cells. METHODS: In this study, total RNA was extracted from MMQ cells and MMQ tumor stem-like cells...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28161597/angiogenesis-related-genes-and-thalidomide-teratogenesis-in-humans-an-approach-on-genetic-variation-and-review-of-past-in-vitro-studies
#16
Thayne Woycinck Kowalski, Lucas Rosa Fraga, Luciana Tovo-Rodrigues, Maria Teresa Vieira Sanseverino, Mara Helena Hutz, Lavínia Schuler-Faccini, Fernanda Sales Luiz Vianna
Thalidomide embryopathy (TE) has affected more than 10,000 babies worldwide. The hypothesis of antiangiogenesis as the teratogenic mechanism of thalidomide has been investigated in several experimental models; but, in humans, it has only been accessed by in vitro studies. Here, we hypothesized the effect of thalidomide upon angiogenesis-related molecules or proteins, previously identified in human embryonic cells, through the in silico STRING-tool. We also investigated ten polymorphisms in angiogenesis-related genes in 38 Brazilian TE individuals and 136 non-affected Brazilians...
February 1, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28151770/organ-specific-differences-in-endothelial-permeability-regulating-molecular-responses-in-mouse-and-human-sepsis
#17
Adnan Aslan, Matijs van Meurs, Jill Moser, Eliane R Popa, Rianne M Jongman, Peter J Zwiers, Grietje Molema, Jan G Zijlstra
In patients with sepsis-induced MODS, diverging patterns of oedema formation and loss of function in organs such as lung and kidney suggest that endothelial permeability-regulating molecular responses are differentially regulated. This potential differential regulation has been insufficiently studied at the level of components of adherens and tight junctions. We hypothesized that such a regulation by endothelial cells in sepsis takes place in an organ-specific manner. We addressed our hypothesis by studying by quantitative RT-PCR the expression of a predefined subset of EC permeability-related molecules (occludin, claudin-5, PV-1, CD-31, endomucin, Angiopoietin-1, Angiopoietin-2, Tie2, VEGFA, VEGFR1, VEGFR2, and VE-cadherin) in kidney and lung after systemic LPS injection in mice, and in kidneys of patients who died of sepsis...
February 1, 2017: Shock
https://www.readbyqxmd.com/read/28147320/association-of-vegfa-polymorphisms-with-susceptibility-and-clinical-outcome-of-hepatocellular-carcinoma-in-a-chinese-han-population
#18
Fei Liu, Limei Luo, Yonggang Wei, Wentao Wang, Tianfu Wen, Jiayin Yang, Mingqing Xu, Bo Li
Vascular endothelial growth factor A (VEGFA) is an important angiogenesis regulator, which plays an important role in angiogenesis and progression of tumor, including hepatocellular carcinoma (HCC). We aimed at determining whether single nucleotide polymorphisms of VEGFA gene influence the development and clinical outcomes of HCC. We analyzed four potential functional polymorphisms (936C/T, 634G/C, 1612G/A, 2578C/A) of VEGFA gene in 476 HCC patients and 526 controls using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28131600/mir-126-overexpression-inhibits-high-glucose-induced-migration-and-tube-formation-of-rhesus-macaque-choroid-retinal-endothelial-cells-by-obstructing-vegfa-and-pik3r2
#19
Wen-Zhi Yang, Jin Yang, Li-Ping Xue, Li-Bo Xiao, Yan Li
AIM: The aims of this study are to investigate the relative regulation between miR-126 and VEGF/PI3K/AKT signaling pathway in retinal vascular endothelial cells. METHODS: Rhesus macaque choroid-retinal endothelial cell line (RF/6A) cells were cultured in high glucose to imitate the conditions occurring in DR. First, we detected the expression of miR-126, VEGFA and PIK3R2 in RF/6A cells on the condition of high glucose by q-PCR and western blot. Then, after addition of miR-126 mimics and miR-126 inhibitor, we investigated the function of miR-126 in RF/6A cells by scratch wound, Transwell migration and tube formation assays, and the effect of miR-126 on the expression of VEGFA, PIK3R2 and AKT...
December 23, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28124845/identification-of-neuron-related-genes-for-cell-therapy-of-neurological-disorders-by-network-analysis
#20
Li-Ning Su, Xiao-Qing Song, Hui-Ping Wei, Hai-Feng Yin
Bone mesenchymal stem cells (BMSCs) differentiated into neurons have been widely proposed for use in cell therapy of many neurological disorders. It is therefore important to understand the molecular mechanisms underlying this differentiation. We screened differentially expressed genes between immature neural tissues and untreated BMSCs to identify the genes responsible for neuronal differentiation from BMSCs. GSE68243 gene microarray data of rat BMSCs and GSE18860 gene microarray data of rat neurons were received from the Gene Expression Omnibus database...
2017: Journal of Zhejiang University. Science. B
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