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https://www.readbyqxmd.com/read/28930752/salivary-gland-neoplasms-does-morphological-diversity-reflect-tumor-heterogeneity
#1
Miguel Rito, Isabel Fonseca
Salivary gland tumor classification encompasses a vast list of benign and malignant neoplasms. Their morphological diversity is recognized not only between different entities but also within individual tumors. Tumor categories as described by the World Health Organization reflect, in part, a true genetic heterogeneity (e.g., translocations involving CRTC1 and CRTC3-MAML2 genes in mucoepidermoid carcinoma and MYB-NFIB fusion in adenoid cystic carcinoma). Carcinoma ex pleomorphic adenoma shows diversity in its histological appearance, but recurrent rearrangements on PLAG1 and HMGA2 are common to its benign precursor...
September 21, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28875276/epigenetic-and-genetic-landscape-of-uterine-leiomyomas-a-current-view-over-a-common-gynecological-disease
#2
Antonio Simone Laganà, Daniele Vergara, Alessandro Favilli, Valentina Lucia La Rosa, Andrea Tinelli, Sandro Gerli, Marco Noventa, Amerigo Vitagliano, Onofrio Triolo, Agnese Maria Chiara Rapisarda, Salvatore Giovanni Vitale
PURPOSE: Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas...
September 5, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28852061/cd271-determines-migratory-properties-of-melanoma-cells
#3
Josefine Radke, Florian Roßner, Torben Redmer
Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. However, the contributing role of the receptor in melanoma cell migration is elusive. Here, we explored extracranial (skin, soft tissue, lymph node and liver, n = 13) and matched brain metastases (BM, n = 12) and observed a heterogeneous distribution of phenotypically distinct subsets of CD271(+) cells. In addition, we observed that CD271 expression gradually rises along with melanoma progression and metastasis by exploration of publicly available expression data of nevi, primary melanoma (n = 31) and melanoma metastases (n = 54)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844127/direct-conversion-of-human-umbilical-cord-blood-into-induced-neural-stem-cells-with-sox2-and-hmga2
#4
Jae-Jun Kim, Ji-Hee Shin, Kyung-Rok Yu, Byung-Chul Lee, Insung Kang, Jin Young Lee, Da-Hyun Kim, Yoojin Seo, Hyung-Sik Kim, Soon Won Choi, Kyung-Sun Kang
Recent advances have shown the direct reprogramming of mouse and human fibroblasts into induced neural stem cells (iNSCs) without passing through an intermediate pluripotent state. Thus, direct reprogramming strategy possibly provides a safe and homogeneous cellular platform. However, the applications of iNSCs for regenerative medicine are limited by the restricted availability of cell sources. Human umbilical cord blood (hUCB) cells hold great potential in that immunotyped hUCB units can be immediately obtained from public banks...
August 31, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28839463/tgf%C3%AE-1-promotes-gemcitabine-resistance-through-regulating-the-lncrna-let-nf90-mir-145-signaling-axis-in-bladder-cancer
#5
Junlong Zhuang, Lan Shen, Lin Yang, Xiaojing Huang, Qun Lu, Yangyan Cui, Xi Zheng, Xiaozhi Zhao, Dianzheng Zhang, Ruimin Huang, Hongqian Guo, Jun Yan
High tumor recurrence is frequently observed in patients with urinary bladder cancers (UBCs), with the need for biomarkers of prognosis and drug response. Chemoresistance and subsequent recurrence of cancers are driven by a subpopulation of tumor initiating cells, namely cancer stem-like cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment remains largely unclear. In this study, we found that during gemcitabine treatment lncRNA-Low Expression in Tumor (lncRNA-LET) was downregulated in chemoresistant UBC, accompanied with the enrichment of CSC population...
2017: Theranostics
https://www.readbyqxmd.com/read/28833526/perinatal-lead-pb-exposure-results-in-sex-and-tissue-dependent-adult-dna-methylation-alterations-in-murine-iap-transposons
#6
L Montrose, C Faulk, J Francis, D C Dolinoy
Epidemiological and animal data suggest that adult chronic disease is influenced by early-life exposure-induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic- and activity-related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of four representative IAPs in adult mice exposed to human physiologically relevant levels of Pb two weeks prior to mating through lactation...
August 19, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28830677/hmga2-upregulation-mediates-cd-induced-migration-and-invasion-in-a549%C3%A2-cells-and-in-lung-tissues-of-mice
#7
Huiyuan Luo, Zhiguo Li, Hong Ge, Dan Mei, Lian Zhao, Liping Jiang, Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Jun Cao
Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 μM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice...
August 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28814752/oncofetal-hmga2-effectively-curbs-unconstrained-and-dna-supercoiling
#8
Xiaodan Zhao, Sabrina Peter, Peter Dröge, Jie Yan
HMGA2 belongs to the family of the high mobility group (HMG) proteins. It binds DNA via three AT-hook domains to the minor groove of adenine-thymine (AT) rich DNA. Recently, a new function of HMGA2 as a replication fork chaperone that protects stem and cancer cells from replication fork collapse induced by chemotherapeutic agents was uncovered, suggesting a previously uncharacterized binding at replication forks. In this study, we examined HMGA2 binding to four DNA structures relevant to replication forks, namely ds DNA, ss DNA, forked DNA and supercoiled DNA plectonemes...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802150/mir-let-7a-regulates-anti-citrullinated-protein-antibody-induced-macrophage-activation-and-correlates-with-the-development-of-experimental-rheumatoid-arthritis
#9
Wei Zhu, Jianbo Yu, Shou Qiu, Haifeng Liu, Yan Wang, Xiaoyan Xu, Lili Shao, Lingling Zhu, Yan Jiao, Fan Liu, Xiaodong Zhu
Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA...
August 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28796236/genetic-disruption-of-the-oncogenic-hmga2-plag1-igf2-pathway-causes-fetal-growth-restriction
#10
Walid Abi Habib, Frédéric Brioude, Thomas Edouard, James T Bennett, Anne Lienhardt-Roussie, Frédérique Tixier, Jennifer Salem, Tony Yuen, Salah Azzi, Yves Le Bouc, Madeleine D Harbison, Irène Netchine
PurposeFetal growth is a complex process involving maternal, placental and fetal factors. The etiology of fetal growth retardation remains unknown in many cases. The aim of this study is to identify novel human mutations and genes related to Silver-Russell syndrome (SRS), a syndromic form of fetal growth retardation, usually caused by epigenetic downregulation of the potent fetal growth factor IGF2.MethodsWhole-exome sequencing was carried out on members of an SRS familial case. The candidate gene from the familial case and two other genes were screened by targeted high-throughput sequencing in a large cohort of suspected SRS patients...
August 10, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28768505/tough-decoy-targeting-of-predominant-let-7-mirna-species-in-adult-human-hematopoietic-cells
#11
Jaira F de Vasconcellos, Colleen Byrnes, Y Terry Lee, Joshua M Allwardt, Megha Kaushal, Antoinette Rabel, Jeffery L Miller
BACKGROUND: In humans, the heterochronic cascade composed of the RNA-binding protein LIN28 and its major target, the let-7 family of microRNAs (miRNAs), is highly regulated during human erythroid ontogeny. Additionally, down-regulation of the let-7 miRNAs in cultured adult CD34(+) cells or the over-expression of LIN28 in cultured erythrocytes from pediatric patients with HbSS genotype causes increased levels of fetal hemoglobin (HbF) in the range of 19-40% of the total. Therefore, we hypothesized that focused targeting of individual let-7 miRNA family members would exhibit regulatory effect on HbF expression in human adult erythroblasts...
August 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28765279/the-long-noncoding-rna-hulc-promotes-liver-cancer-by-increasing-the-expression-of-the-hmga2-oncogene-via-sequestration-of-the-microrna-186
#12
Yuan Wang, Fuquan Chen, Man Zhao, Zhe Yang, Jiong Li, Shuqin Zhang, Weiying Zhang, Lihong Ye, Xiaodong Zhang
The long noncoding RNA highly up-regulated in liver cancer (HULC) is aberrantly elevated in hepatocellular carcinoma (HCC), and this up-regulation is crucial for HCC pathogenesis. However, the underlying mechanism in HULC up-regulation is poorly understood. We hypothesized that HULC might modulate the oncogene high mobility group A2 (HMGA2) to promote hepatocarcinogenesis. Quantitative real-time PCR analysis showed that the expression levels of HULC were positively correlated with those of HMGA2 in clinical HCC tissues...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28752530/hmga2-regulates-lung-cancer-proliferation-and-metastasis
#13
Xiaotian Gao, Ming Dai, Qinglan Li, Zhigang Wang, Yonglin Lu, Zeqing Song
BACKGROUND: This study aimed to explore the effects of HMGA2 on cell proliferation and metastases in lung cancer and its underlying mechanism. METHODS: HMGA2 expression in lung cancer tissues and its association with overall survival were analyzed based on data from a public database. The roles of HMGA2 were validated via loss-of-function and gain-of-function experiments in vitro. HMGA2 regulation by microRNA-195 (miR-195) was validated by real time-PCR, Western blotting, and luciferase reporter assays...
September 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28720546/the-lncrna-neat1-facilitates-cell-growth-and-invasion-via-the-mir-211-hmga2-axis-in-breast-cancer
#14
Xuerui Li, Shuxia Wang, Zhenzhong Li, Xiaoyu Long, Zibai Guo, Guochun Zhang, Jian Zu, Yu Chen, Linzhu Wen
Long non-coding RNAs play a significant role in cancer metastasis. Studies have demonstrated that LncRNA NEAT1 promotes cancer progression. We aimed to explore whether NEAT1 regulated growth and invasion in breast cancer cells. We provided evidence that lncRNA NEAT1 was up-regulated in breast cancer cell lines and tissues. NEAT1 promoted invasion through inducing Epithelial-mesenchymal transition (EMT) and NEAT1 played a role in 5-fluorouracil (5-FU) resistance. In addition, we revealed a reciprocal repression between NEAT1 and miR-211...
July 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28714014/microrna-219-is-downregulated-in-non-small-cell-lung-cancer-and-inhibits-cell-growth-and-metastasis-by-targeting-hmga2
#15
Xiaoping Sun, Min Xu, Haiyan Liu, Kunxiu Ming
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and accounts for ~85% of all lung cancer cases. An increasing number of studies suggest that microRNAs (miRs) may be involved in the regulation of NSCLC carcinogenesis and progression. However, the expression and function of miRNA-219 in NSCLC, and its underlying mechanisms of action, remain unknown. In the present study, miR-219 expression in NSCLC tissues and cell lines was determined using reverse transcription-quantitative polymerase chain reaction...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713923/the-differential-regulation-of-micrornas-is-associated-with-oral-cancer
#16
Shih-Chang Tsai, Sheng-Fong Huang, Jo-Hua Chiang, Yen-Fu Chen, Chia-Chang Huang, Ming-Hsui Tsai, Fuu-Jen Tsai, Ming-Ching Kao, Jai-Sing Yang
Oral squamous cell carcinoma (OSCC), is the most frequently occurring malignant head and neck tumor, generally it exhibits a poor prognosis, and metastasis is the main cause of death in these cancer patients. The discovery of reliable prognostic indicators for tumors progression would greatly improve clinical treatments. MicroRNAs (miRNAs) play a critical role in the degradation of mRNA and the inhibition of protein synthesis. The miRNAs function either as tumor suppressors or as oncogenes in tumorigenesis, and little is known about the clinical significance of miRNA expression profiles in oral cancers...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28710822/prevalence-and-significance-of-hmga2-expression-in-esophageal-adenocarcinoma
#17
Jeffrey K Mito, Agoston T Agoston, Paola Dal Cin, Amitabh Srivastava
AIMS: Esophageal adenocarcinoma (EAC) tumorigenesis has been primarily linked to loss-of-function mutations in tumor suppressor genes. Knowledge of specific oncogenes that drive tumor progression, and their relationship to outcomes, is limited. High Mobility Group AT-Hook 2 (HMGA2) has been reported to be amplified in a subset of EACs, but the clinicopathologic and prognostic implications of HMGA2 expression in EAC is unknown. METHODS AND RESULTS: We performed HMGA2 immunohistochemistry and fluorescence in-situ hybridization (FISH) in EAC to determine its clinicopathologic and prognostic significance...
July 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28708584/clinicopathological-and-prognostic-significance-of-hmga2-overexpression-in-gastric-cancer-a-meta-analysis
#18
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...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28691642/xiap-3-untranslated-region-serves-as-a-competitor-for-hmga2-by-arresting-endogenous-let-7a-5p-in-human-hepatocellular-carcinoma
#19
Wen-Yong Wu, Si-Qi Tao, Xiao-Nan Wang, Peter E Lobie, Zheng-Sheng Wu
X-linked inhibitor of apoptosis protein functions as an intrinsic regulator of apoptosis by inhibition of caspase activity and possesses a pivotal role in human cancer development and progression. A growing body of literature has demonstrated that microRNAs lead to the degradation or translational repression of messenger RNAs by binding to the non-coding region of messenger RNA at the 3'-untranslated region. Here, we revealed that the expression of HMGA2 is upregulated with X-linked inhibitor of apoptosis protein after transfection of X-linked inhibitor of apoptosis protein 3'-untranslated region in hepatocellular carcinoma cells, suggesting that X-linked inhibitor of apoptosis protein 3'-untranslated region serves as a competitor for microRNAs and prevent the co-targeted messenger RNA, HMGA2, from being suppressed...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28652867/scattered-genomic-amplification-in-dedifferentiated-liposarcoma
#20
Nils Mandahl, Linda Magnusson, Jenny Nilsson, Björn Viklund, Elsa Arbajian, Fredrik Vult von Steyern, Anders Isaksson, Fredrik Mertens
BACKGROUND: Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes CDK4, HMGA2 and MDM2 from 12q, but often also sequences from other chromosomes...
2017: Molecular Cytogenetics
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