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Sabine Wächter, Annette Wunderlich, Silvia Roth, Ioannis Mintziras, Elisabeth Maurer, Sebastian Hoffmann, Frederik A Verburg, Sebastian A Fellinger, Katharina Holzer, Detlef K Bartsch, Pietro Di Fazio
The prognosis of anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC) is poor, due to their radioiodine refractoriness (RAI-R), high metastatic potential and current lack of effective treatment strategies. We aimed to examine the efficacy of the tyrosine kinase inhibitors (TKIs) sorafenib and selumetinib and the histone deacetylase inhibitor (HDACI) panobinostat in patient-derived tumor tissue (PDTT) of ATCs/PDTCs, the expression of sodium iodide symporter ( NIS ) and radioiodine up-take (RAI-U)...
May 15, 2018: Journal of Clinical Medicine
Zhenpeng Qiu, Junxuan Zhou, Cong Zhang, Ye Cheng, Junjie Hu, Guohua Zheng
An abnormality in the Lin28/let-7a axis is relevant to the progression of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be a novel therapeutic target for this malignant tumor. The present study aimed to investigate the antiproliferative and anti-invasive effects of urolithin A in a stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and transwell assays. The RNA and protein expressions of targets were assessed by quantitative PCR and western blot, respectively...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Jaewook Chung, Xia Zhang, Bruce Collins, Renan B Sper, Katherine Gleason, Sean Simpson, Sehwon Koh, Jeffrey Sommer, William L Flowers, Robert M Petters, Jorge A Piedrahita
Expression of HMGA2 is strongly associated with body size and growth in mice and humans. In mice, inactivation of one or both alleles of Hmga2 results in body-size reductions of 20% and 60%, respectively. In humans, microdeletions involving the HMGA2 locus result in short stature, suggesting the function of the HMGA2 protein is conserved among mammals. To test this hypothesis, we generated HMGA2-deficient pigs via gene editing and somatic cell nuclear transfer (SCNT). Examination of growth parameters revealed that HMGA2 -/+ male and female pigs were on average 20% lighter and smaller than HMGA2 +/+ matched controls ( P < 0...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shanshan Zhang, Huibian Zhang, Lin Yu
To identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan-Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP-qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co-immunoprecipitation were applied to identify HMGA2-activated target sites, which were further verified by mRNA and protein expression detection...
May 7, 2018: Cancer Medicine
Wentao Tang, Pingping Xu, Hong Wang, Zhengchuan Niu, Dexiang Zhu, Qi Lin, Liming Tang, Li Ren
Background: Growing evidence suggests that miR-150 plays an inhibitory role in various types of cancer. However, the function and underlying mechanisms of miR-150 in triple-negative breast cancer (TNBC) remain unknown. Patients and methods: miR-150 expression was detected by qRT-PCR and ISH in TNBC tumor and adjacent normal breast tissues. miR-150 function was analyzed by wound healing and transwell assay in vitro and mouse lung metastasis model in vivo. mRNA microarray, qRT-PCR, western blotting and luciferase assay were used to identify the target gene of miR-150 ...
2018: OncoTargets and Therapy
Yasushi Takahashi, Kaname Uno, Katsunori Iijima, Yasuhiko Abe, Tomoyuki Koike, Naoki Asano, Kiyotaka Asanuma, Tooru Shimosegawa
Gastric cancer (GC) after eradication for Helicobacter pylori ( H.pylori ) increases, but its carcinogenesis is not elucidated. It is mainly found in acid non-secretion areas (ANA), as mucosal regeneration in acid secretory areas (AA) after eradication changes the acidity and bile toxicity of gastric juice. We aimed to clarify the role of barrier dysfunction of ANA by the stimulation of pH3 bile acid cocktail (ABC) during carcinogenesis. We collected 18 patients after curative endoscopic resection for GC, identified later than 24 months after eradication, and took biopsies by Congo-red chromoendoscopy to distinguish AA and ANA (UMIN00018967)...
April 6, 2018: Oncotarget
Osamu Baba, Takahiro Horie, Tetsushi Nakao, Daihiko Hakuno, Yasuhiro Nakashima, Hitoo Nishi, Yasuhide Kuwabara, Masataka Nishiga, Tomohiro Nishino, Yuya Ide, Fumiko Nakazeki, Satoshi Koyama, Masahiro Kimura, Ritsuko Hanada, Masahiro Kawahara, Takeshi Kimura, Koh Ono
MicroRNA (miR)-33 targets ATP-binding cassette transporter A1 (ABCA1), and its deficiency increases serum HDL-cholesterol (HDL-C) and ameliorates atherosclerosis. Although we previously reported that miR-33 deficiency increased peripheral Ly6Chigh monocytes on ApoE-deficient background, the effect of miR-33 on monocyte population is not fully elucidated especially on wild-type (WT) background.We found that Ly6Chigh monocytes in miR-33-/- mice were decreased in peripheral blood and increased in bone marrow (BM)...
April 30, 2018: Molecular and Cellular Biology
Chenglai Xia, Shaofeng Liang, Zhihong He, Xiaolan Zhu, Ruihong Chen, Jinman Chen
The molecular mechanisms underlying the anti-neoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. To explore the novel anti-neoplastic mechanisms of metformin, the transwell chamber and wound-healing assays were used to evaluate its effects on the migration and invasion of human cervical cancer cells. Real-time PCR and Western blotting were used to measure the gene and protein expression, respectively, of microRNA (miRNA) miR-142-3p, long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), and high-mobility group AT-hook 2 (HMGA2)...
April 25, 2018: European Journal of Pharmacology
Ioannis Panagopoulos, Ludmila Gorunova, Marius Lund-Iversen, Kristin Andersen, Hege Kilen Andersen, Ingvild Lobmaier, Bodil Bjerkehagen, Sverre Heim
BACKGROUND: Spindle cell/pleomorphic lipomas are benign tumors. Here, we present our cytogenetic data on 31 such tumors. MATERIALS AND METHODS: G-banding chromosome analysis and (in selected cases) fluorescence in situ hybridization (FISH) using probes for FOXO1, RB1, and HMGA2 were performed. RESULTS: Rearrangements of chromosome 13 were found in 58% of tumors. Chromosomes 6, 1, 12, and 11 were also involved in 42%, 26%, 26%, and 23% of tumors, respectively...
May 2018: Cancer Genomics & Proteomics
Ying Yang, Hua Jiang, Ling Xiao, Xuezhou Yang
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease, but its pathogenesis remains largely unknown. The present study explored the role of microRNA‑33b‑5p (miR‑33b‑5p) in PCOS pathogenesis, with a particular focus on its role in regulating glucose transporter 4 (GLUT4). A rat model of PCOS was developed by injecting female SD rats with insulin and HCG. miR‑33b‑5p, GLUT4, sterol regulatory element‑binding protein 1 (SREBF1), and high mobility group A2 (HMGA2) expression in rat ovarian tissues was examined by qRT‑PCR and immunohistochemistry...
April 18, 2018: Oncology Reports
Hua-Sheng Chiu, María Rodríguez Martínez, Elena V Komissarova, David Llobet-Navas, Mukesh Bansal, Evan O Paull, José Silva, Xuerui Yang, Pavel Sumazin, Andrea Califano
microRNAs (miRNAs) play key roles in cancer, but their propensity to couple their targets as competing endogenous RNAs (ceRNAs) has only recently emerged. Multiple models have studied ceRNA regulation, but these models did not account for the effects of co-regulation by miRNAs with many targets. We modeled ceRNA and simulated its effects using established parameters for miRNA/mRNA interaction kinetics while accounting for co-regulation by multiple miRNAs with many targets. Our simulations suggested that co-regulation by many miRNA species is more likely to produce physiologically relevant context-independent couplings...
April 19, 2018: Nucleic Acids Research
Xinzhi Liu, Yimamu Yidayitula, Heng Zhao, Yi Luo, Xiaoqiang Ma, Minhua Xu
Long non-coding RNAs (lncRNAs) LINC00152 plays important roles in the progression of some tumors. However, the role of LINC00152 in human l glioblastoma is still unknown. In this study, we indicated that LINC00152 expression level was upregulated in glioblastoma tissues and cell lines. Overexpression of LINC00152 promoted the U87 and LN229 cell proliferation and invasion. Moreover, overexpression of LINC00152 suppressed the E-cadherin expression, where ectopic expression of LINC00152 promoted the N-cadherin, Vimentin, and Snail expression...
April 18, 2018: Environmental Science and Pollution Research International
Li Xu, Bin Du, Qi-Jue Lu, Xiao-Wen Fan, Ke Tang, Lie Yang, Wei-Lin Liao
An increasing number of studies have demonstrated that micro-ribonucleic acids (miRNAs) are important tumor suppressors during carcinogenesis. However, the function of miRNA-541 (miR-541) in malignancies, especially lung cancer, has not been widely reported. In this study, miR-541 expression was significantly decreased in squamous cell lung carcinoma (SCLC) cancerous tissue and SCLC cell lines. To analyze miR-541 function in SCLC, we overexpressed miR-541 in SCLC cell lines (SK-MES-1 and H226). According to the CCK8, wound scratch, and transwell invasion assay results, miR-541 overexpression significantly inhibited SCLC cell proliferation, migration, and invasion ability...
April 16, 2018: Cancer Medicine
Gloria Sarah Leszinski, Katharina Warncke, Julia Hoefele, Matias Wagner
Patients with Silver-Russell syndrome (SRS), a syndromic growth retardation syndrome, usually harbor a maternal uniparental disomy of chromosome 7 or an epimutation at chromosome 11p15. However, to date the genetic cause remains unknown in around 40% of SRS cases, suggesting genetic heterogeneity and involvement of other genes. We present a 4-year-old female patient with the clinical diagnosis of SRS and negative results in common genetic SRS diagnostics. Whole exome sequencing identified a de novo heterozygous 7...
April 12, 2018: Gene
N Gao, F-X Wang, G Wang, Q-S Zhao
OBJECTIVE: Previous study reported that miR-498 served as a tumor suppressor in non-small cell lung cancer (NSCLC), but the underlying mechanism remains largely unknown. The aim of this study is to investigate the role of miR-498 and its target gene HMGA2 in NSCLC progression. PATIENTS AND METHODS: The expression of miR-498 was assessed in clinical NSCLC specimens and cell lines using RT-PCR. Overexpression of miR-498 and transfection of pLenti-HMGA2 were performed in A549 cells...
March 2018: European Review for Medical and Pharmacological Sciences
Marcella Cesana, Michael H Guo, Davide Cacchiarelli, Lara Wahlster, Jessica Barragan, Sergei Doulatov, Linda T Vo, Beatrice Salvatori, Cole Trapnell, Kendell Clement, Patrick Cahan, Kaloyan M Tsanov, Patricia M Sousa, Barbara Tazon-Vega, Adriano Bolondi, Federico M Giorgi, Andrea Califano, John L Rinn, Alexander Meissner, Joel N Hirschhorn, George Q Daley
While gene expression dynamics have been extensively cataloged during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators...
April 5, 2018: Cell Stem Cell
Hannah C Beird, Chia-Chin Wu, Davis R Ingram, Wei-Lien Wang, Asrar Alimohamed, Curtis Gumbs, Latasha Little, Xingzhi Song, Barry W Feig, Christina L Roland, Jianhua Zhang, Robert S Benjamin, Patrick Hwu, Alexander J Lazar, P Andrew Futreal, Neeta Somaiah
Well-differentiated (WD) liposarcoma is a low-grade mesenchymal tumor with features of mature adipocytes and high propensity for local recurrence. Often, WD patients present with or later progress to a higher-grade nonlipogenic form known as dedifferentiated (DD) liposarcoma. These DD tumors behave more aggressively and can metastasize. Both WD and DD liposarcomas harbor neochromosomes formed from amplifications and rearrangements of Chr 12q that encode oncogenes ( MDM2 , CDK4 , and YEATS2) and adipocytic differentiation factors ( HMGA2 and CPM) However, genomic changes associated with progression from WD to DD have not been well-defined...
April 2018: Cold Spring Harbor Molecular Case Studies
Ting Xi, Guizhi Zhang
BACKGROUND: Tumor differentiation is an important process in the development of cancer. It is valuable to identify key differentiation related genes in the prognosis and therapy of pancreatic adenocarcinoma. METHODS: The mRNA expression data were downloaded from the Cancer Genome Atlas database. Then, differentially expressed tumor differentiation related genes were identified. Additionally, Gene Ontology functional categories and Kyoto Encyclopedia of Genes and Genomes biochemical pathway was used to explore the function...
2018: PloS One
Yanzhuo Luo, Bingjin Li, Guangxin Zhang, Yuxiao He, Jeeyoo Hope Bae, Fengping Hu, Ranji Cui, Runhua Liu, Zhou Wang, Lizhong Wang
Targeted therapies based on EGFR mutations or on the ALK fusion oncogene have become the standard treatment for certain patients with lung adenocarcinoma (LUAD). However, most LUAD patients have no EGFR mutation or ALK fusion, and their oncogenetic alterations remain to be characterized. Here we conducted an integrated analysis of public datasets to assess the genomic alterations of 23 highly lung cancer-associated genes. The copy numbers of these genes were measured in ten micro-dissected, paired tumors and normal lung tissues of LUAD patients without EGFR mutations or ALK fusion...
2018: Journal of Cancer
Hailing Zhao, Huizhen Zhao, Xiaolin Xia, Xiujuan Liu
Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of clear cell renal cell carcinoma (ccRCC) through their participation in a number of critical biological processes. Therefore, an in‑depth investigation into miRNAs and their biological roles within ccRCC may provide useful insights and lead to the identification of novel therapeutic methods for patients with ccRCC. miRNA‑599 (miR‑599) serves critical roles in different types of human cancer. However, the expression pattern, biological function and molecular mechanism of miR‑599 in ccRCC remain unknown...
March 15, 2018: Molecular Medicine Reports
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