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miR-34a

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https://www.readbyqxmd.com/read/27917453/phase-i-study-of-mrx34-a-liposomal-mir-34a-mimic-administered-twice-weekly-in-patients-with-advanced-solid-tumors
#1
Muhammad S Beg, Andrew J Brenner, Jasgit Sachdev, Mitesh Borad, Yoon-Koo Kang, Jay Stoudemire, Susan Smith, Andreas G Bader, Sinil Kim, David S Hong
Purpose Naturally occurring tumor suppressor microRNA-34a (miR-34a) downregulates the expression of >30 oncogenes across multiple oncogenic pathways, as well as genes involved in tumor immune evasion, but is lost or under-expressed in many malignancies. This first-in-human, phase I study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical activity of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumors. Patients and Methods Adult patients with solid tumors refractory to standard treatment were enrolled in a standard 3 + 3 dose escalation trial...
December 5, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27911398/evaluation-of-bioenergetic-function-in-cerebral-vascular-endothelial-cells
#2
Stephanie L Rellick, Heng Hu, James W Simpkins, Xuefang Ren
The integrity of the blood-brain-barrier (BBB) is critical to prevent brain injury. Cerebral vascular endothelial (CVE) cells are one of the cell types that comprise the BBB; these cells have a very high-energy demand, which requires optimal mitochondrial function. In the case of disease or injury, the mitochondrial function in these cells can be altered, resulting in disease or the opening of the BBB. In this manuscript, we introduce a method to measure mitochondrial function in CVE cells by using whole, intact cells and a bioanalyzer...
November 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27893432/microrna-34a-expression-levels-in-serum-and-intratumoral-tissue-can-predict-bone-metastasis-in-patients-with-hepatocellular-carcinoma
#3
Zuo-Lin Xiang, Xiao-Mei Zhao, Li Zhang, Ping Yang, Jia Fan, Zhao-You Tang, Zhao-Chong Zeng
Hepatocellular carcinoma (HCC) patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. We screened a microRNA (miRNA) microarray to identify potential serum biomarkers for BM in HCC patients. A miRNA microarray was used to screen for BM-related miRNAs in paired serum samples from HCC patients with BM and from HCC patients without BM. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to quantify candidate miRNAs in serum samples from 106 independent HCC patients...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889881/identification-of-reference-genes-and-mirnas-for-qrt-pcr-in-human-esophageal-squamous-cell-carcinoma
#4
Li Chen, Yulin Jin, Lin Wang, Fenghao Sun, Xiaodong Yang, Mengkun Shi, Cheng Zhan, Yu Shi, Qun Wang
It is important to select an appropriate reference gene and miRNA when using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze gene and miRNA expression. However, many commonly used reference genes and miRNAs are not stably expressed and therefore not suitable for normalization or quantification of qRT-PCR data. This study aims to identify appropriate reference genes and miRNAs for use in human esophageal squamous carcinoma qRT-PCR analysis. Using data provided by The Cancer Genome Atlas, we identified DDX5, LAPTM4A, P4HB, RHOA, miR-28-5p, miR-34a-5p, and miR-186-5p as candidate reference genes and miRNAs...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27889708/mir-34a-is-a-common-link-in-both-hiv-and-antiretroviral-therapy-induced-vascular-aging
#5
Jiaxin Zhan, Shanshan Qin, Lili Lu, Xiamin Hu, Jun Zhou, Yeying Sun, Jian Yang, Ying Liu, Zunzhe Wang, Ning Tan, Jiyan Chen, Chunxiang Zhang
Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition...
November 26, 2016: Aging
https://www.readbyqxmd.com/read/27885275/tdb-protects-vascular-endothelial-cells-against-oxygen-glucose-deprivation-reperfusion-induced-injury-by-targeting-mir-34a-to-increase-bcl-2-expression
#6
Li-Xi Liao, Ming-Bo Zhao, Xin Dong, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu
Prolonged ischemia can result in apoptotic death of vascular endothelial cells and lead to ischemic vascular diseases including vascular dementia, arteriosclerosis and brain oedema. Finding protective strategies to prevent this is therefore an urgent mission. Recent studies have shown that dysregulation of microRNAs (miRNAs) can lead to imbalance of Bcl-2 family proteins and mitochondrial dysfunction, leading to further damage of vascular cells under ischemic conditions. However, whether miRNAs can be used as a drug target for treating vascular diseases is not fully understood...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879964/decreased-levels-of-mir-34a-and-mir-217-act-as-predictor-biomarkers-of-aggressive-progression-and-poor-prognosis-in-hepatocellular-carcinoma
#7
W Yu, Quan Shen, Qing F Jiang, Yao X Wang, Ke Li, Huan Z Xue
BACKGROUND: MicroRNAs (miRNAs) play key roles in tumor development and progression. The aim of this study was to explore the expression levels of miR-34a and miR-217 in hepatocellular carcinoma (HCC) and to further investigate the clinicopathological and prognostic value of miR-34a and miR-217. METHODS: The expression levels of miR-34a and miR-217 were evaluated using quantitative real-time PCR (qRT-PCR). Associations between these miRNAs expression and clinicopathological features were analyzed...
November 23, 2016: Minerva Medica
https://www.readbyqxmd.com/read/27871116/glucocorticoid-signaling-and-bone-biology
#8
T Komori
Since glucocorticoids remain an effective therapeutic option for the treatment of many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Fractures may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Under physiological conditions, glucocorticoids are required for normal bone development due to their regulation of osteoblast differentiation, possibly via the Wnt/β-catenin pathway and TSC22D3. However, serum levels of endogenous corticosterone are elevated in aged mice and glucocorticoids exert negative effects on the survival of osteoblasts and osteocytes as well as angiogenesis...
November 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27869909/altered-levels-of-circulating-cytokines-and-micrornas-in-lean-and-obese-individuals-with-prediabetes-and-type-2-diabetes
#9
Yury O Nunez Lopez, Gabriella Garufi, Attila A Seyhan
Today obesity and type 2 diabetes (T2D) have both reached epidemic proportions. However, our current understanding of the primary mechanisms leading to these diseases is still limited due to the complex multifactorial nature of the underlying phenomena. We hypothesize that the levels of specific cytokines and miRNAs vary across the diabetes spectrum and unique signatures associated with them may serve as early biomarkers of the disease and provide insights into respective pathogenetic mechanisms. In this study, we measured the circulating levels of cytokines and microRNAs (miRNAs) in lean and obese humans with prediabetes (n = 21), T2D (n = 17), and healthy controls (n = 20) (ORIGINS trial, NCT02226640)...
November 21, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27869139/the-transcription-cofactor-crtc1-protects-from-aberrant-hepatic-lipid-accumulation
#10
Hwijin Kim
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging global health-problem. NAFLD encompasses a range of conditions associated with hepatic steatosis, aberrant accumulation of fat in hepatocytes. Although obesity and metabolic syndrome are considered to have a strong association with NAFLD, genetic factors that predispose liver to NAFLD and molecular mechanisms by which excess hepatic lipid develops remain largely unknown. We report that the transcription cofactor CRTC1 confers broad spectrum protection against hepatic steatosis development...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27858840/regulation-of-podocyte-lesions-in-diabetic-nephropathy-via-mir-34a-in-the-notch-signaling-pathway
#11
Xiangying Zhang, Shuping Song, Huixin Luo
BACKGROUND: The activation of the Notch signaling pathway has been shown to play an important role in diabetic nephropathy (DN) development. Besides, Notch-1 is a target gene in miR-34a. However, the regulation of the podocyte lesions involved in DN by miR-34a has not been identified. METHODS: This study utilized miR-34a mimics and small interfering RNA transfection to construct miR-34a overexpression and lower-expression model to investigate the effect of miR-34a on the regulation of the Notch signaling pathway and podocyte lesions in DN...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27836543/mir-34a-sensitizes-lung-cancer-cells-to-cisplatin-via-p53-mir-34a-mycn-axis
#12
Changshan Song, Pingfang Lu, Guoqiang Sun, Lin Yang, Zhigang Wang, Zheng Wang
Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, a large proportion of NSCLC patients were insensitive to chemotherapy. This study explored the role of miR-34a in regulating sensitivity of NSCLC cells to cisplatin and its downstream targets. The quantitative PCR result showed that miR-34a expression was upregulated in cisplatin sensitive NSCLC patients compared cisplatin insensitive NSCLC controls. By applying loss-and-gain function analysis, we demonstrated that miR-34a directly targeted to MYCN to sensitize NSCLC cells to cisplatin...
November 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27813227/mir-34a-modulates-erbb2-in-breast-cancer
#13
Yilin Wang, Xiaolong Zhang, Zou Chao, Hsiang-Fu Kung, Marie C Lin, Andreas Dress, Fiona Wardle, Bing-Hua Jiang, Lihui Lai
Breast cancer is the second highest cause of carcinoma-related death caused by distant metastasis in women. Estrogen receptor (ER), human epidermal growth factor receptor 2, (HER2) and progesterone receptor (PR) are three classified makers of breast cancer, which are defined as ER+, HER2+, and the most serious ER-PR-HER2- (triple-negative). It is well known that ErbB2 (V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog 2) plays an important part in breast cancer. However, the molecular mechanisms underlying ErbB2 action needs to be well studied...
November 4, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27805929/genetic-variant-rs3750625-in-the-3-utr-of-adra2a-affects-stress-dependent-acute-pain-severity-after-trauma-and-alters-a-microrna-34a-regulatory-site
#14
Sarah D Linnstaedt, Margaret G Walker, Kyle D Riker, Jennifer E Nyland, JunMei Hu, Catherine Rossi, Robert A Swor, Jeffrey S Jones, Luda Diatchenko, Andrey V Bortsov, David A Peak, Samuel A McLean
α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs. facilitation after both physical and psychological stress. To our knowledge the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity...
October 25, 2016: Pain
https://www.readbyqxmd.com/read/27804997/a-presenilin-notch1-pathway-regulated-by-mir-375-mir-30a-and-mir-34a-mediates-glucotoxicity-induced-pancreatic-beta-cell-apoptosis
#15
Yating Li, Tao Zhang, Yuncai Zhou, Yi Sun, Yue Cao, Xiaoai Chang, Yunxia Zhu, Xiao Han
The presenilin-mediated Notch1 cleavage pathway plays a critical role in controlling pancreatic beta cell fate and survival. The aim of the present study was to investigate the role of Notch1 activation in glucotoxicity-induced beta cell impairment and the contributions of miR-375, miR-30a, and miR-34a to this pathway. We found that the protein levels of presenilins (PSEN1 and PSEN2), and NOTCH1 were decreased in INS-1 cells after treatment with increased concentrations of glucose, whereas no significant alteration of mRNA level of Notch1 was observed...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27790245/associations-of-mrna-microrna-for-the-shared-downstream-molecules-of-egfr-and-alternative-tyrosine-kinase-receptors-in-non-small-cell-lung-cancer
#16
Fengfeng Wang, Fei Meng, Lili Wang, S C Cesar Wong, William C S Cho, Lawrence W C Chan
Lung cancer is the top cancer killer worldwide with high mortality rate. Majority belong to non-small cell lung cancers (NSCLCs). The epidermal growth factor receptor (EGFR) has been broadly explored as a drug target for therapy. However, the drug responses are not durable due to the acquired resistance. MicroRNAs (miRNAs) are small non-coding and endogenous molecules that can inhibit mRNA translation initiation and degrade mRNAs. We wonder if some downstream molecules shared by EGFR and the other tyrosine kinase receptors (TKRs) further transduce the signals alternatively, and some miRNAs play the key roles in affecting the expression of these downstream molecules...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27789474/p66shc-induced-microrna-34a-causes-diabetic-endothelial-dysfunction-by-downregulating-sirtuin1
#17
Qiuxia Li, Young-Rae Kim, Ajit Vikram, Santosh Kumar, Modar Kassan, Mohanad Gabani, Sang Ki Lee, Julia S Jacobs, Kaikobad Irani
OBJECTIVE: Diabetes mellitus causes vascular endothelial dysfunction and alters vascular microRNA expression. We investigated whether endothelial microRNA-34a (miR-34a) leads to diabetic vascular dysfunction by targeting endothelial sirtuin1 (Sirt1) and asked whether the oxidative stress protein p66Shc governs miR-34a expression in the diabetic endothelium. APPROACH AND RESULTS: MiR-34a is upregulated, and Sirt1 downregulated, in aortic endothelium of db/db and streptozotocin-induced diabetic mice...
October 27, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27784320/sirt1-expression-is-associated-with-cd31-expression-in-blood-cells-from-patients-with-chronic-obstructive-pulmonary-disease
#18
Ryo Kato, Shiro Mizuno, Maiko Kadowaki, Kohei Shiozaki, Masaya Akai, Ken Nakagawa, Taku Oikawa, Masaharu Iguchi, Kazuhiro Osanai, Takeshi Ishizaki, Norbert F Voelkel, Hirohisa Toga
BACKGROUND: Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD)...
October 27, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27780933/ampelopsin-attenuates-brain-aging-of-d-gal-induced-rats-through-mir-34a-mediated-sirt1-mtor-signal-pathway
#19
Xianjuan Kou, Xingran Liu, Xianbing Chen, Jie Li, Xiaoqi Yang, Jingjing Fan, Yi Yang, Ning Chen
The underlying molecular mechanisms for aging-related neurodegenerative diseases such as Alzheimer's disease (AD) are not fully understood. Currently, growing evidences have revealed that microRNAs (miRNAs) are involved in aging and aging-related diseases. The up-regulation of miR-34a has been reported to be associated with aging-related diseases, and thus it should be a promising therapeutic target. Ampelopsin, also called dihydromyricetin (DHM), a natural flavonoid from Chinese herb Ampelopsis grossedentata, has been reported to possess multiple pharmacological functions including anti-inflammatory, anti-oxidative and anti-cancer functions...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27780189/changes-in-the-expression-of-mir-34a-and-its-target-genes-following-spinal-cord-injury-in-rats
#20
Ying Chen, Shuyan Cao, Pingping Xu, Wei Han, Tiankai Shan, Jingying Pan, Weiwei Lin, Xue Chen, Xiaodong Wang
BACKGROUND Results from DNA microarray experiments have shown that the expression of miR-34s undergoes significant changes following spinal cord injury (SCI). The present study was designed to detect changes in the expression of miR-34s and its target genes during the acute and sub-acute stages of SCI. MATERIAL AND METHODS Luxol fast blue (LFB) staining for myelin was used to observe the differences in the general morphology of the spinal cord after SCI in a contusion model in rats. qPCR was carried out to determine the expression variation of miR-34s and its target genes during the acute and sub-acute stages of SCI...
October 25, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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