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Zuping Zhang, Yali Ran, Tanner S Shaw, Yuandong Peng
MicroRNAs are a class of small non-coding RNAs that bind to the three prime untranslated region (3'-UTR) of target mRNAs. They cause a cleavage or an inhibition of the translation of target mRNAs, thus regulating gene expression. Here, we employed three prediction tools to search for potential miRNA target sites in the 3'-UTR of the human platelet glycoprotein (GP) 1BA gene. A luciferase reporter assay shows that miR-10a and -10b sites are functional. When miR-10a or -10b mimics were transfected into the GP Ibβ/GP IX-expressing cells, along with a DNA construct harboring both the coding and 3'-UTR sequences of the human GP1BA gene, we found that they inhibit the transient expression of GP Ibα on the cell surface...
November 9, 2016: International Journal of Molecular Sciences
Qian Fan, Xiangrui Meng, Hongwei Liang, Huilai Zhang, Xianming Liu, Lanfang Li, Wei Li, Wu Sun, Haiyang Zhang, Ke Zen, Chen-Yu Zhang, Zhen Zhou, Xi Chen, Yi Ba
The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6...
November 4, 2016: Protein & Cell
Shuyao Tang, Gang Tan, Xian Jiang, Peng Han, Bo Zhai, Xuesong Dong, Haiquan Qiao, Hongchi Jiang, Xueying Sun
Sorafenib resistance remains a major obstacle for the effective treatment of hepatocellular carcinoma (HCC), and a number of miRNAs contribute to this resistance. However, the regulatory networks of miRNAs are very complex, thus inhibiting a single miRNA may sequentially activate other compensatory pathways. In the present study, we generated an artificial long non-coding RNA (AlncRNA), which simultaneously targets multiple miRNAs including miR-21, miR-153, miR-216a, miR-217, miR-494 and miR-10a-5p. These miRNAs have been shown to be upregulated in sorafenib-resistant cells and participate in the mechanisms underlying sorafenib resistance...
September 28, 2016: Oncotarget
Ye Shu, Qinghua Hu, Hai Long, Christopher Chang, Qianjin Lu, Rong Xiao
Autoimmune diseases are characterized by aberrant immune responses against healthy cells and tissues. However, the exact mechanisms underlying the development of these conditions remain unknown. CD4+CD25+ regulatory T cells (Tregs) are a subset of mature T cells which have an important role in maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box p3 (Foxp3), a member of the fork head transcription factor family, is recognized as a marker of CD4+CD25+ Tregs. The decreased number and/or function of CD4+CD25+ Tregs in peripheral blood and related tissues has been demonstrated in systemic lupus erythematosus, systemic sclerosis, and other autoimmune diseases, which are at least partially regulated by epigenetic mechanisms...
September 29, 2016: Clinical Reviews in Allergy & Immunology
Chunlei Song, Jing Yao, Chunwei Cao, Xiaojuan Liang, Jiaojiao Huang, Ziqiang Han, Yang Zhang, Guosong Qin, Cong Tao, Chengbo Li, Haoran Yang, Jianguo Zhao, Kui Li, Yanfang Wang
To elucidate the key miRNAs and the signalling pathways that are involved in porcine oocyte maturation, we performed a deep sequencing analysis of the miRNAs of pig germinal vesicle (GV) oocytes and metaphase II (MII) oocytes. Seven differentially expressed (DE) miRNAs were identified and the expression levels of miR-21 and miR-27b-3p were further confirmed by QPCR analysis. The target genes of 7 DE miRNAs were predicted and subjected to pathway analysis. Interestingly, fatty acid metabolism and fatty acid biosynthesis were the top two significantly enriched molecular functions during oocyte maturation...
October 14, 2016: Biochemical and Biophysical Research Communications
Veronika Mancikova, Cristina Montero-Conde, Javier Perales-Paton, Agustin F Fernandez, Maria Santacana, Karolina Jodkowska, Lucía Inglada-Pérez, Esmeralda Castelblanco, Salud Borrego, Mario Encinas, Xavier Matias-Guiu, Mario F Fraga, Mercedes Robledo
PURPOSE: Medullary thyroid carcinoma (MTC) is a rare disease with few genetic drivers, and the etiology specific to each known susceptibility mutation remains unknown. Exploiting multilayer genomic data, we focused our interest on the role of aberrant DNA methylation in MTC development. EXPERIMENTAL DESIGN: We performed genome-wide DNA methylation profiling assessing >27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors...
September 12, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Guangyao Zhou, Wei Lin, Peipei Fang, Xiuzhen Lin, Lu Zhuge, Zhiqiu Hu, Lingxiang Jin
The aim of the present study was to examine the expression variation of the mouse hepatic fibrosis tissue transforming growth factor (TGF)-βl/Smads signal transduction pathway and its correlation with progression of hepatic fibrosis. The promotion effect of microRNA (miR)-10a on hepatic fibrosis and its possible mechanism was also assessed. Forty healthy female 8-week-old C57BL6/J mice were randomly divided into the control group (intraperitoneal injection of 5 µl/g normal saline, twice per week for 8 weeks) and the hepatic fibrosis group (intraperitoneal injection of 5 µl/g 10% CCI4 olive oil, twice per week for 8 weeks), with 20 mice per group...
September 2016: Experimental and Therapeutic Medicine
Nicla Borrelli, Maria Denaro, Clara Ugolini, Anello Marcello Poma, Mario Miccoli, Paolo Vitti, Paolo Miccoli, Fulvio Basolo
Follicular variants of papillary thyroid carcinoma include encapsulated (with or without capsular/vascular invasion) and infiltrative forms, which have different clinical behaviors. The encapsulated forms that lack capsular invasion have an indolent clinical behavior that is similar to benign lesions; therefore, they were recently reclassified as 'noninvasive follicular thyroid neoplasms with papillary-like nuclear features' (NIFTPs). Because NIFTPs have nuclear features of papillary carcinomas, distinguishing between NIFTPs and infiltrative follicular variant of papillary thyroid carcinoma is almost impossible with cytological examination...
September 2, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Kaylyn L Devlin, Tiffany Sanford, Lauren M Harrison, Paul LeBourgeois, Laura M Lashinger, Elizabeth Mambo, Stephen D Hursting
MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized...
2016: PloS One
Leda Torres, Ulises Juárez, Laura García, Juan Miranda-Ríos, Sara Frias
There is no information regarding the role of microRNAs in the development of the external ear in mammals. The purpose of this study was to determine the stage-specific expression of microRNA during external ear development in mice under normal conditions. GeneChip miRNA 3.0 arrays by Affymetrix were used to obtain miRNA expression profiles from mice fetal pinnae and back skin tissues at 13.5 days-post-coitum (dpc) and 14.5 dpc. Biological triplicates for each tissue were analyzed; one litter represents one biological replica, each litter had 16 fetuses on average...
September 2016: Genomics Data
Vanmathy Kasimanickam, John Kastelic
Uterine infections in dairy cows are common after calving, reduce fertility and cause substantial economic losses. Conventional diagnosis (based on clinical signs) and treatment can be challenging. Serum microRNA (miRNA) profiles serve as non-invasive biomarkers in several pathological conditions including inflammatory diseases. The objective was to identify differentially expressed serum miRNAs in cows with metritis and normal uterus (four cows per group), integrate miRNAs to their target genes, and categorize target genes for biological processes involved in bacterial infection and inflammatory responses...
2016: Scientific Reports
Liyun Luo, Bairong Chen, Songbiao Li, Xiaoliang Wei, Tianmin Liu, Yin Huang, Xiufang Lin
Aims. MicroRNAs (miRNAs) are involved in the pathogenesis of coronary artery disease (CAD). The objective of this study is to determine plasma levels of miR-10a in CAD and analyze its association with the severity of CAD. Materials and Methods. Plasma miR-10a levels in 60 CAD patients including stable angina pectoris (SAP) (n = 29), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (MI) (NSTEMI) (n = 17), or ST elevation MI (STEMI) (n = 14) and 20 non-CAD subjects were assessed by real-time polymerase chain reaction (qRT-PCR), and associations of miR-10a levels with risk factors of CAD and its severity were analyzed...
2016: Disease Markers
Dongling Zou, Qi Zhou, Dong Wang, Lili Guan, Li Yuan, Shaolin Li
It has been demonstrated that microRNAs (miRNAs) act as oncogenes or tumor suppressors in a variety of cancers. Our previous work suggested that miR-10a/b functioned as a tumor suppressor in gastric cancer, and miR-10b was also reported to be significantly downregulated in advanced stage cervical cancer tissues. However, the aberrant expression of miR-10b in cervical cancer and its possible role in cervical carcinogenesis was largely unknown. In this study, we investigated the expression of miR-10b in cervical cancer tissues, carcinoma in situ tissues, mild dysplasia, moderate dysplasia, severe dysplasia tissues, and normal controls...
2016: Oncology Research
Seung-Chul Choi, Tarun E Hutchinson, Anton A Titov, Howard R Seay, Shiwu Li, Todd M Brusko, Byron P Croker, Shahram Salek-Ardakani, Laurence Morel
Pbx1 controls chromatin accessibility to a large number of genes and is entirely conserved between mice and humans. The Pbx1-d dominant-negative isoform is more frequent in CD4(+) T cells from lupus patients than from healthy controls. Pbx1-d is associated with the production of autoreactive T cells in mice carrying the Sle1a1 lupus-susceptibility locus. Transgenic (Tg) expression of Pbx1-d in CD4(+) T cells reproduced the phenotypes of Sle1a1 mice, with increased inflammatory functions of CD4(+) T cells and impaired Foxp3(+) regulatory T cell (Treg) homeostasis...
July 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Qun Shan, Guihong Zheng, Aihua Zhu, Li Cao, Jun Lu, Dongmei Wu, ZiFeng Zhang, Shaohua Fan, Chunhui Sun, Bin Hu, Yuanlin Zheng
Emerging evidence has shown that microRNA-mediated gene expression modulation plays a crucial role in the pathogenesis of type 2 diabetes mellitus, but the novel miRNAs involved in type 2 diabetes and its functional regulatory mechanisms still need to be determined. In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice...
September 1, 2016: Toxicology and Applied Pharmacology
Yanting Liu, Ningbo Xu, Boyang Liu, Yiru Huang, Huijun Zeng, Zhao Yang, Zhenyan He, Hongbo Guo
Resistance to temolozomide (TMZ), the standard chemotherapy agent for treating glioblastomas (GBM), is a major clinical problem for patients with GBM. Recently, long noncoding RNAs (lncRNAs) have been implicated in chemotherapy resistance in various cancers. In this study, we found that the level of the lncRNA RP11-838N2.4 was lower in TMZ-resistant GBM cells (U87TR, U251TR) compared to the parental, non-resistant GBM cells (U87, U251). In GBM patients, the decreased level of lncRNA RP11-838N2.4 correlated with higher risk of GBM relapse, as well as shorter postoperative survival times...
May 30, 2016: Oncotarget
Chun Wang, Hie-Won Hann, Zhong Ye, Richard S Hann, Shaogui Wan, Xishan Ye, Peter D Block, Bingshan Li, Ronald E Myers, Xiaowei Wang, Hee-Soon Juon, Jesse Civan, Mimi Chang, Ho S Bae, Jinliang Xing, Hushan Yang
The predictive value of circulating microRNAs (miRNAs) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has been demonstrated in retrospective studies, but it has rarely been tested in prospective studies. In a cohort of 373 cancer-free HBV patients with a median follow-up of 4.5 years, we measured the expression of 24 retrospectively identified HCC-related miRNAs in baseline serum samples. When we analyzed the prospective associations of miRNA expression with HCC risk using the Cox proportional hazards model, we found that 15 of the 24 miRNAs exhibited a significant association with HCC risk...
May 24, 2016: Oncotarget
Mengyao Zhou, Guangyuan Yu, Xiantao Yang, Chaomin Zhu, Zhenzhen Zhang, Xue Zhan
MicroRNAs (miRNAs) are a class of highly conserved, single-stranded RNA molecules (length, 18-25 nt) that regulate the expression of their target mRNAs. Previous studies have demonstrated that miRNAs may be novel biomarkers in the diagnosis of certain diseases. In order to evaluate the diagnostic value of miRNAs in childhood tuberculosis (TB), the circulating miRNA profile was determined using microarray analysis. An miRNA‑gene network was constructed to identify closely associated miRNAs and these miRNAs were validated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
June 2016: Molecular Medicine Reports
Naiara C Cinegaglia, Sonia Cristina S Andrade, Tomas Tokar, Maísa Pinheiro, Fábio E Severino, Rogério A Oliveira, Erica N Hasimoto, Daniele C Cataneo, Antônio J M Cataneo, Júlio Defaveri, Cristiano P Souza, Márcia M C Marques, Robson F Carvalho, Luiz L Coutinho, Jefferson L Gross, Silvia R Rogatto, Wan L Lam, Igor Jurisica, Patricia P Reis
Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0...
May 17, 2016: Oncotarget
Yuan Rong, Chun-Hui Yuan, Zhen Qu, Hu Zhou, Qing Guan, Na Yang, Xiao-Hua Leng, Lang Bu, Ke Wu, Fu-Bing Wang
Chemotherapies often induce drug-resistance in cancer cells and simultaneously stimulate proliferation and activation of Myeloid-Derived Suppressor Cells (MDSCs) to inhibit anti-tumor T cells, thus result in poor prognosis of patients with breast cancers. To date, the mechanism underlying the expansion of MDSCs in response to chemotherapies is poorly understood. In the present study, we used in vitro cell culture and in vivo animal studies to demonstrate that doxorubicin-resistant breast cancer cells secret significantly more prostaglandin E2 (PGE2) than their parental doxorubicin-sensitive cells...
2016: Scientific Reports
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