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HMGA2

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https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#1
Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman
BACKGROUND: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. RESULTS: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522832/the-fragment-hmga2-sh-3p20-from-hmga2-mrna-3-utr-promotes-the-growth-of-hepatoma-cells-by-upregulating-hmga2
#2
Yuan Wang, Fuquan Chen, Zhe Yang, Man Zhao, Shuqin Zhang, Yuen Gao, Jinyan Feng, Guang Yang, Weiying Zhang, Lihong Ye, Xiaodong Zhang
High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3'-untranslated region (3'UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3'UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514723/genomic-profiling-of-pelvic-genital-type-leiomyosarcoma-in-a-woman-with-a-germline-chek2-c-1100delc-mutation-and-a-concomitant-diagnosis-of-metastatic-invasive-ductal-breast-carcinoma
#3
My Linh Thibodeau, Caralyn Reisle, Eric Zhao, Lee Ann Martin, Yazeed Alwelaie, Karen L Mungall, Carolyn Ch'ng, Ruth Thomas, Tony Ng, Stephen Yip, Howard Lim, Sophie Sun, Sean S Young, Aly Karsan, Yongjun Zhao, Andrew J Mungall, Richard A Moore, Daniel Renouf, Karen Gelmon, Yussanne P Ma, Malcolm Hayes, Janessa Laskin, Marco A Marra, Kasmintan A Schrader, Steven J M Jones
INTRODUCTION: We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumour suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximate 2-fold increase in breast cancer risk...
May 16, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28510366/hmga2-plays-an-important-role-in-cr-vi-induced-autophagy
#4
Fan Yang, Lian Zhao, Dan Mei, Liping Jiang, Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Yong Liu, Ying Kong, Jun Cao
Cr (VI) is mutagenic and carcinogenic, but the mechanism is unclear. In this study, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-induced autophagy was investigated. Cr (VI) treatment induced formation of autophagosomes, increased expression of LC3II, Atg12-Atg5, Atg4, Atg10, HMGA1 and HMGA2 proteins, and decreased the expression of p62 in A549 cells. Silencing of HMGA2 gene by siRNA blocked Cr (VI)-induced formation of autophagosomes, expression of LC3II, Atg12-Atg5, Atg10 and reduction of p62...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28502886/hmga2-a-driver-of-inflammation-is-associated-with-hypermethylation-in-acute-liver-injury
#5
Huimin Huang, Haidi Li, Xin Chen, Yang Yang, Xiaofeng Li, Wanxia Li, Cheng Huang, Xiaoming Meng, Lei Zhang, Jun Li
Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs as a driver at critical stage of hepatocellular carcinoma, herein, we investigated the role of HMGA2 in macrophage activation during ALI. Our study found that the expression of HMGA2 decreased dramatically both in KCs isolated from the liver in mice with ALI and in LPS-induced RAW264...
May 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#6
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28487599/mir-195-regulates-proliferation-and-apoptosis-through-inhibiting-the-mtor-p70s6k-signaling-pathway-by-targeting-hmga2-in-esophageal-carcinoma-cells
#7
Yong Li, Dapeng Wu, Pei Wang, Xiaohui Li, Gongning Shi
miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated...
2017: Disease Markers
https://www.readbyqxmd.com/read/28474175/the-hmga-gene-family-in-chordates-evolutionary-perspectives-from-amphioxus
#8
Matteo Bozzo, Simone Macrì, Daniela Calzia, Riccardo Sgarra, Guidalberto Manfioletti, Paola Ramoino, Thurston Lacalli, Robert Vignali, Mario Pestarino, Simona Candiani
High mobility group A proteins of vertebrates, HMGA1 and 2, are chromatin architectural factors involved in development, cell differentiation, and neoplastic transformation. Here, we characterize an amphioxus HMGA gene ortholog and analyze its expression. As a basal chordate, amphioxus is well placed to provide insights into the evolution of the HMGA gene family, particularly in the transition from invertebrates to vertebrates. Our phylogenetic analysis supports the basal position of amphioxus, echinoderm, and hemichordate HMGA sequences to those of vertebrate HMGA1 and HMGA2...
May 4, 2017: Development Genes and Evolution
https://www.readbyqxmd.com/read/28469731/integrated-data-analysis-reveals-potential-drivers-and-pathways-disrupted-by-dna-methylation-in-papillary-thyroid-carcinomas
#9
Caroline Moraes Beltrami, Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fabio Albuquerque Marchi, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28463429/hmga2-is-a-specific-immunohistochemical-marker-for-pleomorphic-adenoma-and-carcinoma-ex-pleomorphic-adenoma
#10
Jeffrey K Mito, Vickie Y Jo, Simion I Chiosea, Paola Dal Cin, Jeffrey F Krane
AIMS: Accurate classification of salivary gland neoplasms may be challenging due to morphologic overlap, particularly in small biopsies. Recurrent translocations involving High Mobility Group A2 (HMGA2) are present in a subset of pleomorphic adenoma (PA) and carcinoma ex-pleomorphic adenoma (CA ex-PA). We evaluated immunohistochemical HMGA2 expression in 225 salivary gland tumors including 56 PAs, 37 CA ex-PAs and 132 potential histologic mimics to determine its diagnostic utility. METHODS AND RESULTS: HMGA2 expression was identified in 19 PAs (33...
April 30, 2017: Histopathology
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#11
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442558/gene-flow-ancient-polymorphism-and-ecological-adaptation-shape-the-genomic-landscape-of-divergence-among-darwin-s-finches
#12
Fan Han, Sangeet Lamichhaney, B Rosemary Grant, Peter R Grant, Leif Andersson, Matthew T Webster
Genomic comparisons of closely related species have identified "islands" of locally elevated sequence divergence. Genomic islands may contain functional variants involved in local adaptation or reproductive isolation and may therefore play an important role in the speciation process. However, genomic islands can also arise through evolutionary processes unrelated to speciation, and examination of their properties can illuminate how new species evolve. Here, we performed scans for regions of high relative divergence (FST) in 12 species pairs of Darwin's finches at different genetic distances...
April 25, 2017: Genome Research
https://www.readbyqxmd.com/read/28436711/mir-33b-5p-sensitizes-gastric-cancer-cells-to-chemotherapy-drugs-via-inhibiting-hmga2-expression
#13
Xiaoyan Yang, Qian Zhao, Huali Yin, Xiaoyong Lei, Runliang Gan
MicroRNAs (miRNAs) are internal, noncoding, and ∼22 nt small RNAs that display cell- and tissue-specific expression. They play important regulatory roles in cell proliferation and chemo-sensitivity. This study focused on tumor-suppressive miR-33b-5p expression as well as its role in gastric cancer. MiR-33b-5p was found low expression in gastric cancer cell lines. Functionally, western blots and the luciferase reporter assay were used to confirme that HMGA2 was the potential target of miR-33b-5p. Next, we used CCK-8 kits to analyze the effect of miR-33b-5p combined chemotherapy drugs on cell inhibition rate, and flow cytometry to analyze cells apoptosis...
April 24, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28423547/genomic-imbalances-are-involved-in-mir-30c-and-let-7a-deregulation-in-ovarian-tumors-implications-for-hmga2-expression
#14
Antonio Agostini, Marta Brunetti, Ben Davidson, Claes G Tropé, Sverre Heim, Ioannis Panagopoulos, Francesca Micci
The High-mobility group AT-hook 2 protein (HMGA2) is involved in different processes during tumorigenesis. High expression levels of HMGA2 are found in various types of cancer, with recent studies highlighting the important role of miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas) analyzed for HMGA2 expression as well as the expression of two miRNAs targeting this gene, let-7a and miR-30c. We also evaluated the expression of the fragile histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to be an enhancer of miR-30c expression and a repressor of let-7a, respectively...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420321/submucosal-colonic-lipoblastoma-presenting-with-colo-colonic-intussusception-in-an-infant
#15
Marie-Anne Brundler, Kyle C Kurek, Kamlesh Patel, Ingo Jester
Lipoblastoma is a benign adipose tumor typically presenting in infancy in superficial soft tissues of extremities. Intestinal complications secondary to intraabdominal or retroperitoneal involvement are exceedingly rare. We describe a unique case of a primary intestinal lipoblastoma arising from the submucosa of the transverse colon in an otherwise healthy 18-month-old boy. He presented with a history of reducible rectal prolapse, rectal bleeding, and episodic abdominal pain and was initially treated for constipation...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28415789/hmga2-translocation-induced-in-skin-tumorigenesis
#16
Yong Li, Xiang-Ying Pi, Kelsey Boland, Sonali Lad, Kelly Johnson, Catherine Verfaillie, Rebecca J Morris
Hmga2 protein, a transcription factor involved in chromatin architecture, is expressed chiefly during development, where it has many key biological functions. When expressed in adult tissues from in various organs, Hmga2 is always related to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not yet understood. We demonstrated that Hmga2 can be found in non-transformed epidermis, specifically located to the membrane of keratinocytes (KCs) in epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and TPA mouse models was associated with translocation of the Hmga2 protein from the membrane into the nucleus, where Hmga2 induced its own expression by binding to the Hmga2 promoter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407409/clinical-and-molecular-characterization-of-a-second-family-with-the-12q14-microdeletion-syndrome-and-review-of-the-literature
#17
Rita Fischetto, Orazio Palumbo, Federica Ortolani, Pietro Palumbo, Maria Pia Leone, Francesco Andrea Causio, Sabino Pesce, Maria Christina Digilio, Massimo Carella, Francesco Papadia
The 12q14 microdeletion syndrome is a rare condition characterized by low birth weight, failure to thrive, short stature, learning disabilities, and osteopoikilosis. To date, 20 cases of 12q14 deletion have been reported in the literature, displaying both phenotypic than genetic variability. We report on three familial cases, a mother and two brothers, with severe short stature. The mother and elder brother presented with osteopoikilosis while the younger brother had severe short stature and developmental delay...
April 13, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28407177/mrna-and-protein-expression-levels-of-four-candidate-genes-for-ear-size-in-erhualian-and-large-white-pigs
#18
L C Zhang, J Liang, L Pu, Y B Zhang, L G Wang, X Liu, H Yan, L X Wang
Porcine ear size is an important characteristic for distinguishing among pig breeds. In a previous genome-wide association study of porcine ear size, LEM domain-containing 3 (LEMD3), methionine sulfoxide reductase B3 (MSRB3), high mobility group AT-hook 2 (HMGA2), and Wnt inhibitory factor 1 (WIF1) were implicated as important candidate genes for ear size. This study investigated the expression levels of four candidate genes for ear size in Erhualian and Large White pigs. Ten Erhualian pigs with large ears and eight Large White pigs with small ears at 60 days of age were examined...
April 13, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28400788/the-lin28-let-7-pathway-in-cancer
#19
REVIEW
Julien Balzeau, Miriam R Menezes, Siyu Cao, John P Hagan
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28395339/nutritional-programming-of-accelerated-puberty-in-heifers-alterations-in-dna-methylation-in-the-arcuate-nucleus%C3%A2-%C3%A2
#20
Bruna R C Alves, Rodolfo C Cardoso, Ryan Doan, Youwen Zhang, Scott V Dindot, Gary L Williams, Marcel Amstalden
High rates of body weight gain during the juvenile period appear to program molecular events within the hypothalamus, leading to advancement of puberty. Methylation of DNA, an epigenetic mechanism that controls gene expression, is associated with metabolic programming events and is proposed to play a role in the pubertal process. In this study, DNA methylation was assessed in genomic DNA obtained from the arcuate nucleus (ARC) of juvenile heifers fed to gain body weight at low (0.5 kg/d; low-gain, LG, n = 4) or high (1 kg/d; high-gain, HG, n = 4) rates from 4...
January 1, 2017: Biology of Reproduction
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