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Jie-Ning Zhu, Yong-Heng Fu, Zhi-Qin Hu, Wen-Yu Li, Chun-Mei Tang, Hong-Wen Fei, Hui Yang, Qiu-Xiong Lin, De-Ming Gou, Shu-Lin Wu, Zhi-Xin Shan
The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells...
September 19, 2017: Scientific Reports
Hyunjoo Kwon, Kyoungsub Song, Chang Han, Jinqiang Zhang, Lu Lu, Weina Chen, Tong Wu
Aberrant expression and regulation of miRNAs have been implicated in multiple stages of tumorigenic processes. The current study was designed to explore the biological function and epigenetic regulation of miR-34a in human cholangiocarcinoma (CCA). Our data show that the expression of miR-34a is decreased significantly in CCA cells compared with non-neoplastic biliary epithelial cells. Forced overexpression of miR-34a in CCA cells inhibited their proliferation and clonogenic capacity in vitro, and suppressed tumor xenograft growth in severe combined immunodeficiency mice...
October 2017: American Journal of Pathology
Xianping Dai, Mengshun Li, Feng Geng
Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. q-PCR analysis revealed that miR-34a could be significantly induced by PUFAs in U266 and primary MM cells. Transfection with miR-34a antagonist or miR-34a agomir could restore or suppress the dexamethasone sensitivity in U266 cells...
July 2017: Biochemistry. Biokhimii︠a︡
Xiaojia Huang, Xinhua Xie, Hua Wang, Xiangsheng Xiao, Lu Yang, Zhi Tian, Xiaofang Guo, Lijuan Zhang, Hailin Tang, Xiaoming Xie
BACKGROUD: The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a. METHODS: Western blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them...
September 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
Li Gu, Jason Z Deng, Sweta Roy, Paula T Hammond
PURPOSE: Mutation of the Kirsten ras sarcoma viral oncogene homolog (KRAS) and loss of p53 function are commonly seen in non-small cell lung cancer (NSCLC). Combining therapeutics targeting these tumor defensive pathways with cisplatin in a single nanoparticle platform are rarely developed in clinic. EXPERIMENTAL DESIGN: Cisplatin was encapsulated in liposomes which multiple polyelectrolyte layers including siKRAS and miR-34a were built on to generate multifunctional layer-by-layer nanoparticle...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yu-Jin Lee, Yeong-Rim Kang, So Young Lee, Yena Jin, Dong Cho Han, Byoung-Mog Kwon
Ginkgetin has been reported to display antitumor activity. However, the relevant pathway integrating cell cycle regulation and signaling pathways involved in growth inhibition in CRC cells remains to be identified. In this study, ginkgetin-treated HCT116 CRC cells exhibited significant dose-dependent growth inhibition with a GI50 value of 4.0 µM for 48-h treatment, together with apoptosis, via G2-phase cell cycle arrest. When HCT116 cells were treated with 10 µM ginkgetin for 48 h, the percentage of cells in G2/M phase increased by 2...
September 5, 2017: International Journal of Oncology
Yunxia Wang, Kongxi Zhu, Weihua Yu, Hongjuan Wang, Lan Liu, Qiong Wu, Shuai Li, Jianqiang Guo
Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model...
September 9, 2017: Biochemical and Biophysical Research Communications
Ying Zhang, Gang Liu, Xiaogang Gao
MicroRNAs (miRNAs) are a class of endogenous, short single-stranded non-coding RNAs, which are tightly linked to cardiac disorders such as myocardial ischemia/reperfusion (I/R) injury. MiR-34a is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclear. In this study, we demonstrate under low glucose supply, rat cardiomyocytes are susceptive to hypoxia. Under short time hypoxia, cellular glucose uptake and lactate product are induced but under long time hypoxia, the cellular glucose metabolism are suppressed...
September 11, 2017: Bioscience Reports
Xiufen Wang, Yucui Xie, Jing Wang
Aberrant expressions of microRNAs (miRNAs) are involved in the development and progression of various types of cancers.In this study, we investigated the roles of miR-34a-5p in proliferation, migration, invasion and apoptosis of cervical cancer cells (HeLa cells). We found that overexpression of miR-34a-5p significantly inhibited the viabilities, migration, and invasion of HeLa cells, but promoted cell apoptosis. Suppression of miR-34a-5p showed opposite effects. The expression levels of Bcl-2 in HeLa cells were increased by miR-34a-5p suppression but decreased by miR-34a-5p overexpression...
August 30, 2017: Oncology Research
Xiaoli Peng, Hui Chang, Junli Chen, Qianyong Zhang, Xiaoping Yu, Mantian Mi
BACKGROUND: Breast cancer is the common cancer in China. In previous study, we determined that 3,6-dihydroxyflavone (3,6-DHF) increases miR-34a significantly in breast carcinogenesis, but the mechanism remains unclear. METHODS: We used qRT-PCR to analyze miR-34a and ten-eleven translocation (TET)1, TET2, TET3 levels in breast cancer cells. With a cellular breast carcinogenesis model and an experimental model of carcinogenesis in rats, TET1 levels were evaluated by western blot analysis and immunofluorescence...
September 5, 2017: BMC Cancer
Zaishun Jin, Tao Zhan, Jing Tao, Biao Xu, Huizhe Zheng, Yongxia Cheng, Bin Yan, Hongwei Wang, Guoqiang Lu, Ying Lin, Sufen Guo
The function of microRNA-34a (miR-34a) in transdifferentiation of glioma stem cells (GSCs) into vascular endothelial cells (VECs) was explored by focusing on Notch ligand Delta-like 1 (Dll1). MiR-34a mimics was transfected into CD133 + glioma cell U251. The angiogenesis feature of miR-34a transfected U251 cells was investigated and the expressions of CD31, CD34, Vwf, Notch 1, and Dll1 were quantified. Length of branching vessel-like structures in the miR-34a transfected U251 cells was significantly higher than control cells...
September 1, 2017: Bioscience, Biotechnology, and Biochemistry
Michaela Mueller, Rui E Castro, Anders Thorell, Hanns-Ulrich Marschall, Nicole Auer, Merima Herac, Cecilia M P Rodrigues, Michael Trauner
BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) is a secondary hydrophilic bile acid (BA) used as therapy for a range of hepatobiliary diseases. Its efficacy in non-alcoholic fatty liver disease (NAFLD) is still under debate. Here we aimed to decipher molecular mechanisms of UDCA in regulating endoplasmic reticulum (ER) homeostasis, apoptosis and oxidative stress in morbidly obese patients. METHODS: In this randomized controlled pharmacodynamic study, liver and serum samples from 40 well-matched morbidly obese NAFLD-patients were analyzed...
August 29, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
Hongying Wei, Fan Liang, Wei Cheng, Ren Zhou, Xiaomeng Wu, Yan Feng, Yan Wang
Fine particulate matter (PM2.5 ) is a major component of air pollutions that are closely associated with increased risk of lung cancer. However, the role of PM2.5 in the etiology of lung cancer is largely unknown. In this study, we performed acute (24 hours) and chronic (five passages) exposure models to investigate the carcinogenetic mechanisms of PM2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties in human non-small cell lung cancer cell line A549...
August 28, 2017: Environmental Toxicology
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Ewelina Semik, Tomasz Zabek, Maciej Wnuk
Methyltransferase DNMT2 is suggested to be involved in the regulation of numerous processes, however its biological significance and underlying molecular mechanisms remain elusive. In the present study, we have used WI-38 and BJ human fibroblasts as an in vitro model system to investigate the effects of siRNA-based DNMT2 silencing. DNMT2-depleted cells were found to be sensitive to oxidative stress conditions as judged by increased production of reactive oxygen species and susceptible to DNA damage that resulted in the inhibition of cell proliferation...
August 18, 2017: Redox Biology
Yi-Fan Tao, Jun Qiang, Guo-Jun Yin, Pao Xu, Qiong Shi, Jing-Wen Bao
MicroRNAs (miRNAs) play vital roles in modulating diverse metabolic processes in the liver, including lipid metabolism. Genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture species in China, is susceptible to hepatic steatosis when reared in intensive culture systems. To investigate the miRNAs involved in GIFT lipid metabolism, two hepatic small RNA libraries from high-fat diet-fed and normal-fat diet-fed GIFT were constructed and sequenced using high-throughput sequencing technology...
August 31, 2017: Fish & Shellfish Immunology
Julian Krauskopf, Theo M de Kok, Dennie G Hebels, Ingvar A Bergdahl, Anders Johansson, Florentin Spaeth, Hannu Kiviranta, Panu Rantakokko, Soterios A Kyrtopoulos, Jos C Kleinjans
Persistent organic pollutants (POPs) are synthetic chemical substances that accumulate in our environment. POPs such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) have been classified as carcinogenic to humans and animals. Due to their resistance to biodegradation humans are still exposed to these compounds worldwide. We aim to evaluate the miRNA and transcriptomic response of a human population exposed to POPs. The miRNA and transcriptomic response was measured in blood of healthy subjects by microarray technology and associated with the serum concentrations of six PCB congeners, DDE (a common DDT metabolite), and HCB...
August 23, 2017: Scientific Reports
Dasa Bohaciakova, Tereza Renzova, Veronika Fedorova, Martin Barak, Michaela Kunova Bosakova, Ales Hampl, Lukas Cajanek
Human embryonic stem cells (hESCs) represent promising tool to study functions of genes during development, to model diseases, and to even develop therapies when combined with gene editing techniques such as CRISPR/Cas9 system. However, the process of disruption of gene expression by generation of null alleles is often inefficient and tedious. To circumvent these limitations, we developed a simple and efficient protocol to permanently downregulate expression of gene of interest in hESCs using CRISPR/Cas9. We selected p53 for our proof of concept experiments...
August 23, 2017: Stem Cells and Development
Angela Jones, Kirsty M Danielson, Miles C Benton, Olivia Ziegler, Ravi Shah, Richard S Stubbs, Saumya Das, Donia Macartney-Coxson
OBJECTIVE: Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. METHODS: One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated...
August 21, 2017: Obesity
Felipe Magalhães Furtado, Priscila Santos Scheucher, Bárbara Amélia Santana, Dalila Lucíola Zanette, Rodrigo do Tocantins Calado, Eduardo Magalhães Rego, Daniel Mazza Matos, Roberto Passetto Falcão
BACKGROUND: Evidence suggests that monoclonal B-cell lymphocytosis precedes all chronic lymphocytic leukemia cases, although the molecular mechanisms responsible for disease progression are not understood. Aberrant miRNA expression may contribute to the pathogenesis of chronic lymphocytic leukemia. The objective of this study was to compare miRNA expression profiles of patients with Binet A chronic lymphocytic leukemia with those of subjects with high-count monoclonal B-cell lymphocytosis and healthy volunteers (controls)...
July 2017: Revista Brasileira de Hematologia e Hemoterapia
Y-L Li, X-M Liu, C-Y Zhang, J-B Zhou, Y Shao, C Liang, H-M Wang, Z-Y Hua, S-D Lu, Z-L Ma
MicroRNAs (miRNAs) are vital in the regulation of tumor progression and invasion. Dysregulation of miRNAs has been linked to the development of various types of human cancers, including non-small-cell lung cancer (NSCLC). However, the effect of miRNA-34a (miR-34a), a key regulator of tumor suppression, on the tumorigenesis of NSCLC has not been fully elaborated. Herein, we reveal that miR-34a is significantly downregulated in NSCLC tissues and cell lines, suggesting that miR-34a might function as a tumor suppressor in lung cancer...
August 21, 2017: Oncogenesis
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