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https://www.readbyqxmd.com/read/29309628/genome-wide-association-study-of-offspring-birth-weight-in-86-577-women-identifies-five-novel-loci-and-highlights-maternal-genetic-effects-that-are-independent-of-fetal-genetics
#1
Robin N Beaumont, Nicole M Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C Richmond, Lavinia Paternoster, Jonathan P Bradfield, Eskil Kreiner-Møller, Ville Huikari, Sarah Metrustry, Kathryn L Lunetta, Jodie N Painter, Jouke-Jan Hottenga, Catherine Allard, Sheila J Barton, Ana Espinosa, Julie A Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J Berry, Luigi Bouchard, Shikta Das, Hakon Hakonarson, Jani Heikkinen, Øyvind Helgeland, Berthold Hocher, Albert Hofman, Hazel M Inskip, Samuel E Jones, Manolis Kogevinas, Penelope A Lind, Letizia Marullo, Sarah E Medland, Anna Murray, Jeffrey C Murray, Pål R Njølstad, Ellen A Nohr, Christoph Reichetzeder, Susan M Ring, Katherine S Ruth, Loreto Santa-Marina, Denise M Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A Tuke, Marc Vaudel, Michael N Weedon, Gonneke Willemsen, Andrew R Wood, Hanieh Yaghootkar, Louis J Muglia, Meike Bartels, Caroline L Relton, Craig E Pennell, Leda Chatzi, Xavier Estivill, John W Holloway, Dorret I Boomsma, Grant W Montgomery, Joanne M Murabito, Tim D Spector, Christine Power, Marjo-Ritta Järvelin, Hans Bisgaard, Struan Fa Grant, Thorkild Ia Sørensen, Vincent W Jaddoe, Bo Jacobsson, Mads Melbye, Mark I McCarthy, Andrew T Hattersley, M Geoffrey Hayes, Timothy M Frayling, Marie-France Hivert, Janine F Felix, Elina Hyppönen, William L Lowe, David M Evans, Debbie A Lawlor, Bjarke Feenstra, Rachel M Freathy
Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects...
January 3, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29307852/global-gene-expression-analysis-of-knockdown-triosephosphate-isomerase-tpi-gene-in-human-gastric-cancer-cell-line-mgc-803
#2
Ping Ouyang, Bode Lin, Jinlin Du, Haiyan Pan, Haibing Yu, Rongwei He, Zhigang Huang
Our preview studies showed TPI gene which encodes the Triosephosphate isomerase was overexpressed in human gastric cancer (GC) tissues. However, the potential molecular mechanisms how TPI influences the GC development is not clear. Here, we performed global gene expression profiling for TPI knockdown using microarrays in human GC cell line MGC-803 cells. The differentially expressed genes (DEGs) were identified using reverse transcription-quantitative polymerase chain reaction analysis. Then the DEGs were analyzed by an online software WebGestalt to perform the functional analysis, pathway analysis and network analysis...
January 4, 2018: Gene
https://www.readbyqxmd.com/read/29296743/hmga2-collaborates-with-jak2v617f-in-the-development-of-myeloproliferative-neoplasms
#3
Koki Ueda, Kazuhiko Ikeda, Takayuki Ikezoe, Kayo Harada-Shirado, Kazuei Ogawa, Yuko Hashimoto, Takahiro Sano, Hiroshi Ohkawara, Satoshi Kimura, Akiko Shichishima-Nakamura, Yuichi Nakamura, Yayoi Shikama, Tsutomu Mori, Philip J Mason, Monica Bessler, Soji Morishita, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Shuhei Koide, Kazumasa Aoyama, Motohiko Oshima, Atsushi Iwama, Yasuchika Takeishi
High-mobility group AT-hook 2 (HMGA2) is crucial for the self-renewal of fetal hematopoietic stem cells (HSCs) but is downregulated in adult HSCs via repression by MIRlet-7 and the polycomb-recessive complex 2 (PRC2) including EZH2. The HMGA2 messenger RNA (mRNA) level is often elevated in patients with myelofibrosis that exhibits an advanced myeloproliferative neoplasm (MPN) subtype, and deletion of Ezh2 promotes the progression of severe myelofibrosis in JAK2V617F mice with upregulation of several oncogenes such as Hmga2...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29281678/the-natural-compound-jatrophone-interferes-with-wnt-%C3%AE-catenin-signaling-and-inhibits-proliferation-and-emt-in-human-triple-negative-breast-cancer
#4
Iram Fatima, Ikbale El-Ayachi, Ling Taotao, M Angeles Lillo, Raya Krutilina, Tiffany N Seagroves, Tomasz W Radaszkiewicz, Miroslav Hutnan, Vitezslav Bryja, Susan A Krum, Fatima Rivas, Gustavo A Miranda-Carboni
Metastatic breast cancer is the leading cause of worldwide cancer-related deaths among women. Triple negative breast cancers (TNBC) are highly metastatic and are devoid of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) amplification. TNBCs are unresponsive to Herceptin and/or anti-estrogen therapies and too often become highly chemoresistant when exposed to standard chemotherapy. TNBCs frequently metastasize to the lung and brain. We have previously shown that TNBCs are active for oncogenic Wnt10b/β-catenin signaling and that WNT10B ligand and its downstream target HMGA2 are predictive of poorer outcomes and are strongly associated with chemoresistant TNBC metastatic disease...
2017: PloS One
https://www.readbyqxmd.com/read/29278873/increased-high-mobility-group-a2-correlates-with-lymph-node-metastasis-and-prognosis-of-non-small-cell-lung-cancer
#5
Xiangjun Guo, Jiaxin Shi, Yan Wen, Mengmeng Li, Qin Li, Xiaomei Li, Jiashu Li
BACKGROUND: High-mobility group A2 (HMGA2) has been investigated to be associated with tumorigenesis; however, the expression pattern and clinical significance of HMGA2 in non-small cell lung cancer (NSCLC) remains poorly understood. The purpose of this study is to examine the expression of HMGA2 and to analyze its relationships with respect to clinico-pathological features and patient survival in NSCLC. METHODS: The expression level of HMGA2 was examined by Western blot and immunohistochemistry in NSCLC cells and tissues...
December 15, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29262356/nanoscale-assembly-of-high-mobility-group-at-hook-2-protein-with-dna-replication-fork
#6
Natalie Krahn, Markus Meier, Vu To, Evan P Booy, Kevin McEleney, Joe D O'Neil, Sean A McKenna, Trushar R Patel, Jörg Stetefeld
High mobility group AT-hook 2 (HMGA2) protein is composed of three AT-hook domains. HMGA2 expresses at high levels in both embryonic stem cells and cancer cells, where it interacts with and stabilizes replication forks (RFs), resulting in elevated cell proliferation rates. In this study, we demonstrated that HMGA2 knockdown reduces cell proliferation. To understand the features required for interaction between HMGA2 and RFs, we studied the solution structure of HMGA2, free and in complex with RFs, using an integrated host of biophysical techniques...
December 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29245994/clinicopathological-and-prognostic-significance-of-hmga2-overexpression-in-gastric-cancer-a-meta-analysis
#7
Jingyi Zhu, Hailong Wang, Shuangnian Xu, Yingxue Hao
Background: High mobility group protein A2 (HMGA2) overexpression has been reported to be closely related to tumor progression [1-4] and indicate significantly worse overall survival in gastric cancer [5-8]. However, a final consensus regarding this issue has not yet been reached. Thus, we conducted a meta-analysis to evaluate the association between HMGA2 expression and prognosis of gastric cancer patients. Methods: The Cochrane Library, Embase, PubMed, Web of Science and China Biology Medicine databases were searched to identify eligible literature published prior to September 2016...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207105/microrna-363-3p-inhibits-cell-growth-and-invasion-of-non%C3%A2-small-cell-lung-cancer-by-targeting-hmga2
#8
Chuanfu Jiang, Yang Cao, Ting Lei, Yu Wang, Junfeng Fu, Ze Wang, Zhenyang Lv
Lung cancer is the second most common cancer and is the leading cause of cancer-related death worldwide. For decades, increasing evidence revealed that microRNAs may contribute to non‑small cell lung cancer (NSCLC) carcinogenesis and progression and could provide novel therapeutic targets for treatments of patients with NSCLC. Accumulated studies indicate that microRNA (miR)‑363‑3p serves important roles in tumorigenesis and tumor development; however, the role of miR‑363‑3p in NSCLC is still unclear...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29193056/identification-of-a-novel-fusion-gene-hmga2-egfr-in-glioblastoma
#9
Akiyoshi Komuro, Erna Raja, Caname Iwata, Manabu Soda, Kazunobu Isogaya, Keiko Yuki, Yasushi Ino, Masato Morikawa, Tomoki Todo, Hiroyuki Aburatani, Hiromichi Suzuki, Melissa Ranjit, Atsushi Natsume, Akitake Mukasa, Nobuhito Saito, Hitoshi Okada, Hiroyuki Mano, Kohei Miyazono, Daizo Koinuma
Glioblastoma is one of the most malignant forms of cancer, for which no effective targeted therapy has been found. Although the Cancer Genome Atlas (TCGA) has provided a list of fusion genes in glioblastoma, their role in progression of glioblastoma remains largely unknown. To search for novel fusion genes, we obtained RNA-seq data from TGS-01 human glioma-initiating cells, and identified a novel fusion gene (HMGA2-EGFR), encoding a protein comprising the N-terminal region of the high mobility group AT hook protein 2 (HMGA2) fused to the C-terminal region of epidermal growth factor receptor (EGFR), which retained the transmembrane and kinase domains of the EGFR...
November 29, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29162914/a-small-molecule-screen-to-identify-regulators-of-let-7-targets
#10
J Cinkornpumin, M Roos, L Nguyen, Xiaoguang Liu, X Gaeta, S Lin, D N Chan, A Liu, R I Gregory, M Jung, J Chute, H Zhu, W E Lowry
The let-7 family of miRNAs has been shown to be crucial in many aspects of biology, from the regulation of developmental timing to cancer. The available methods to regulate this family of miRNAs have so far been mostly genetic and therefore not easily performed experimentally. Here, we describe a small molecule screen designed to identify regulators of let-7 targets in human cells. In particular, we focused our efforts on the identification of small molecules that could suppress let-7 targets, as these could serve to potentially intercede in tumors driven by loss of let-7 activity...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157111/hmga2-cooperates-with-either-p27-kip1-deficiency-or-cdk4-r24c-mutation-in-pituitary-tumorigenesis
#11
Monica Fedele, Orlando Paciello, Davide De Biase, Mario Monaco, Gennaro Chiappetta, Michela Vitiello, Antonio Barbieri, Domenica Rea, Antonio Luciano, Serenella Papparella, Claudio Arra, Alfredo Fusco
We have previously reported a critical role of HMGA proteins in pituitary tumorigenesis since either the Hmga1 or Hmga2 gene overexpression/activation induces the development of mixed growth hormone/prolactin cell pituitary adenomas by activating the E2F transcription factor 1, and then enhancing the G1/S transition of the cell cycle. Consistently, amplification and overexpression of the HMGA2 gene was found in human pituitary prolactinomas. Since impairment of the cell cycle control represents a feature of experimental and human pituitary adenomas, we have investigated the possible synergism between the alterations of other cell cycle regulators, such as p27 deficiency or Cdk4(R24C) mutation, with Hmga2 overexpression in pituitary tumorigenesis...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#12
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138866/hmga2-facilitates-epithelial-mesenchymal-transition-in-renal-cell-carcinoma-by-regulating-the-tgf-%C3%AE-smad2-signaling-pathway
#13
Bo Kou, Wei Liu, Xiaoshuang Tang, Qingshan Kou
High-mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, has been reported to correlate with cancer progression. However, there is no report concerning the correlation between HMGA2 and metastasis in renal cell carcinoma. In the present study, we found that HMGA2 was highly expressed in five renal cell carcinoma cell lines compared with that in the normal renal tubular epithelial HK2 cell line. Additionally, HMGA2 facilitated cell migration and invasion of renal cell carcinoma cells, as evidenced by wound healing and Transwell assays...
November 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29135520/epithelial-myoepithelial-carcinoma-frequent-morphologic-and-molecular-evidence-of-preexisting-pleomorphic-adenoma-common-hras-mutations-in-plag1-intact-and-hmga2-intact-cases-and-occasional-tp53-fbxw7-and-smarcb1-alterations-in-high-grade-cases
#14
Soufiane El Hallani, Aaron M Udager, Diana Bell, Isabel Fonseca, Lester D R Thompson, Adel Assaad, Abbas Agaimy, Alyssa M Luvison, Caitlyn Miller, Raja R Seethala, Simion Chiosea
We hypothesized that there is a relationship between the preexisting pleomorphic adenoma [PA]), histologic grade of epithelial-myoepithelial carcinomas (EMCAs), and genetic alterations. EMCAs (n=39) were analyzed for morphologic and molecular evidence of preexisting PA (PLAG1, HMGA2 status by fluorescence in situ hybridization, FISH, and FGFR1-PLAG1 fusion by next-generation sequencing, NGS). Twenty-three EMCAs were further analyzed by NGS for mutations and copy number variation in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, the following subsets of EMCA emerged: (a) EMCAs with morphologic evidence of preexisting PA, but intact PLAG1 and HMGA2 (12/39, 31%), (b) Carcinomas with PLAG1 alterations (9/39, 23%), or (c) HMGA2 alterations (10/39, 26%), and (d) de novo carcinomas, without morphologic or molecular evidence of PA (8/39, 21%)...
November 9, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29109785/overexpression-of-mir-194-reverses-hmga2-driven-signatures-in-colorectal-cancer
#15
Hsin-Yi Chang, Shu-Ping Ye, Shiow-Lin Pan, Tzu-Ting Kuo, Bia Chia Liu, Yi-Lin Chen, Tsui-Chin Huang
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified...
2017: Theranostics
https://www.readbyqxmd.com/read/29079814/the-role-of-thyroid-transcription-factor-1-and-tumor-differentiation-in-resected-lung-adenocarcinoma
#16
Tsai-Wang Huang, Ke- Feng Lin, Chien-Hsing Lee, Hung Chang, Shih-Chun Lee, Yi-Shing Shieh
To investigate the role of thyroid transcription factor-1 (TTF-1) and tumor differentiation in resected lung adenocarcinoma. A total of 520 patients with clinical early stage lung adenocarcinoma who underwent surgical resection were reviewed retrospectively. Clinical data and outcomes were evaluated with an average follow-up of 117 months. The results were validated via lung cancer cell line studies. The clinical parameters did not differ between relapse and nonrelapse patients. Exceptions were tumor differentiation, lymphovascular space invasion, F(18)-fluorodeoxyglucose maximum standard uptake value, tumor size, and pathological stage (p < 0...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29073636/global-metabolomic-profiling-of-uterine-leiomyomas
#17
Hanna-Riikka Heinonen, Miika Mehine, Netta Mäkinen, Annukka Pasanen, Esa Pitkänen, Auli Karhu, Nanna S Sarvilinna, Jari Sjöberg, Oskari Heikinheimo, Ralf Bützow, Lauri A Aaltonen, Eevi Kaasinen
BACKGROUND: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. METHODS: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy...
October 26, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29066347/jak2v617f-influences-epigenomic-changes-in-myeloproliferative-neoplasms
#18
Chih-Cheng Chen, Chia-Chen Chiu, Kuan-Der Lee, Chia-Chen Hsu, Hong-Chi Chen, Tim H-M Huang, Shu-Huei Hsiao, Yu-Wei Leu
Negative valine (V) to phenylalanine (F) switch at the Janus kinase (JAK2) 617 codon (V617F) is the dominant driver mutation in patients with myeloproliferative neoplasms (MPNs). JAK2V617F was proved to be sufficient for cell transformation; however, independent mutations might influence the following epigenomic modifications. To assess the JAK2V617F-induced downstream epigenomic changes without interferences, we profiled the epigenomic changes in ectopically expressed JAK2V617F in Ba/F3 cells. Antibodies against phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and enhancer of zeste homolog 2 (EZH2) were used for chromatin-immunoprecipitation sequencing (ChIP-seq) to detect the downstream epigenomic targets in the JAK2-STAT3 signaling pathway...
October 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29059722/genome-wide-association-study-reveals-genetic-loci-and-candidate-genes-for-average-daily-gain-in-duroc-pigs
#19
Jianping Quan, Rongrong Ding, Xingwang Wang, Ming Yang, Yang Yang, Enqin Zheng, Ting Gu, Gengyuan Cai, Zhenfang Wu, Dewu Liu, Jie Yang
Objective: Average daily gain (ADG) is an important target trait of pig breeding programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with ADG in the Duroc pig population. Methods: We performed a genome-wide association study involving 390 Duroc boars and by using the PorcineSNP60K Beadchip and two linear models. Results: After quality control, we detected 35971 SNPs, which included seven SNPs that are significantly associated with the ADG of pigs...
October 20, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29055020/subtype-specific-tumor-associated-fibroblasts-contribute-to-the-pathogenesis-of-uterine-leiomyoma
#20
Xin Wu, Vanida Ann Serna, Justin Thomas, Wenan Qiang, Michael L Blumenfeld, Takeshi Kurita
Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here we report the elucidation of the biological characteristics of the two most prevalent LM subtypes, MED12 mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) LM. Since each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-LM were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF)...
October 20, 2017: Cancer Research
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