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Nelly Rahkonen, Aki Stubb, Maia Malonzo, Sanna Edelman, Maheswara Reddy Emani, Elisa Närvä, Harri Lähdesmäki, Hannele Ruohola-Baker, Riitta Lahesmaa, Riikka Lund
MicroRNAs (miRNA) are central regulators of diverse biological processes and are important in the regulation of stem cell self-renewal. One of the widely studied miRNA-protein regulators is the Lin28-Let-7 pair. In this study, we demonstrate that contrary to the well-established models of mouse ES cells (mESC) and transformed human cancer cells, the pluripotent state of human ES cells (hESC) involves expression of mature Let-7 family miRNAs with concurrent expression of all LIN28 proteins. We show that mature Let-7 miRNAs are regulated during hESC differentiation and have opposite expression profile with LIN28B...
September 24, 2016: Stem Cell Research
Suli Huang, Ziquan Lv, Yi Guo, Lu Li, Yanwei Zhang, Li Zhou, Binyao Yang, Shuang Wu, Ying Zhang, Changhui Xie, Shanshan Li, Jinquan Cheng
Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p...
2016: PloS One
Doyeon Kim, You Me Sung, Jinman Park, Sukjun Kim, Jongkyu Kim, Junhee Park, Haeok Ha, Jung Yoon Bae, SoHui Kim, Daehyun Baek
The functional rules for microRNA (miRNA) targeting remain controversial despite their biological importance because only a small fraction of distinct interactions, called site types, have been examined among an astronomical number of site types that can occur between miRNAs and their target mRNAs. To systematically discover functional site types and to evaluate the contradicting rules reported previously, we used large-scale transcriptome data and statistically examined whether each of approximately 2 billion site types is enriched in differentially downregulated mRNAs responding to overexpressed miRNAs...
October 24, 2016: Nature Genetics
Hui Feng, Yalei Wang, Jiaojiao Su, Hongwei Liang, Chen-Yu Zhang, Xi Chen, Weiyan Yao
OBJECTIVES: ErbB3 (HER3) has been associated with pancreatic cancer progression, but little is known about its regulatory mechanisms. We investigated whether microRNAs (miRNAs) regulate levels of ErbB3 in pancreatic cancer cells. METHODS: We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Furthermore, the biological consequences of the targeting of ERBB3 by miR-148a were examined by cell proliferation and migration assays in vitro...
October 2016: Pancreas
Li Wang, Yakui Mou, Deping Meng, Yan Sun, Xiumei Chen, Xin Yang, Chuanliang Jia, Xicheng Song, Xuezhong Li
OBJECTIVE: MicroRNAs play an important role in regulating hypopharyngeal cancer development. miR-203 has been previously shown to possess anti-tumor capabilities in many cancers, but not in hypopharyngeal cancer. DESIGN: Using human normal and hypopharyngeal cancer specimens, we explored the expression levels of miR-203 in the two groups, and further correlated them with different stages of cancer and lymph node metastasis. SETTING AND PARTICIPANTS: Applying human pharynx FaDu cancer cells and lentiviral transduction technique, we investigated the effects of miR-203 on cancer cell viability, migration and invasion...
October 24, 2016: Clinical Otolaryngology
D F Paulo, A M L Azeredo-Espin, L E C Canesin, R Vicentini, A C M Junqueira
MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression through post-transcriptional regulation. Here, we report the identification and characterization of miRNAs in two closely related screwworm flies with different feeding habits: Cochliomyia hominivorax and Cochliomyia macellaria. The New World screwworm, C. hominivorax, is an obligatory parasite of warm-blooded vertebrates, whereas the secondary screwworm, C. macellaria, is a free-living organism that feeds on decaying organic matter. Here, the small RNA transcriptomes of adults and third-instar larvae of both species were sequenced...
October 24, 2016: Insect Molecular Biology
X Liu, X-D Tian, Y Liu, T Zhang, L Chen
OBJECTIVE: It is well documented that some microRNAs (miRNAs) regulates tumorigenesis and cancer metastases of non-small cell lung cancer (NSCLC). Nevertheless, a role of miR-92b in control of the metastasis of NSCLC has not been acknowledged. MATERIALS AND METHODS: Here, we reported that miR-92b levels were significantly decreased and Twist levels were significantly increased in NSCLC specimens, compared to paired adjacent non-tumor lung tissue. Moreover, the levels of miR-92b and Twist inversely correlated...
October 2016: European Review for Medical and Pharmacological Sciences
Y-F Huang, Y Zhang, C-X Liu, J Huang, G-H Ding
OBJECTIVE: Hyperglycemia induces apoptosis of renal tubular epithelial cells and contributes to tubular injury in diabetic nephropathy. Angiotensin-converting enzyme 2 (ACE2) is known to protect against diabetic kidney injury. However, the mechanism for the dysregulation of ACE2 expression in diabetic nephropathy is unclear. MATERIALS AND METHODS: Bioinformatic analysis and luciferase reporter assay were done to identify ACE2-targeting microRNAs. Gain- and loss-of-function experiments were performed to determine the biological roles of the ACE2-targeting microRNAs in high glucose-induced damage to renal tubular epithelial cells...
October 2016: European Review for Medical and Pharmacological Sciences
R-H Xu, B Liu, J-D Wu, Y-Y Yan, J-N Wang
OBJECTIVE: Atherosclerosis is recognized as a chronic inflammatory disease leading to hardening of the vessel wall and narrowing of arteries. Endothelial cells (ECs) exhibit highly active glycolysis, the dysfunction of which leads to accumulation of lipids in the arterial wall and formation of atherosclerotic plaque. MATERIALS AND METHODS: qRT-PCR was performed to compare the deregulated miR-143 between atherosclerotic plaque and normal vessel tissues. The direct target of miR-143 was verified by Western blot and luciferase assay...
October 2016: European Review for Medical and Pharmacological Sciences
H-W Zhang, H Li, H Yan, B-L Liu
OBJECTIVE: MicroRNAs (miRNAs) are small non-coding RNAs (18-25nt) that regulate gene expression mainly through affecting post-transcriptional modification. In this research, the human peripheral blood-derived endothelial progenitor cells were isolated to research the inter-coordination of miR-142, ADAMTS-1, VEGF and eNOS through gene over-expressed in EPCs. MATERIALS AND METHODS: Endothelial progenitor cells (EPCs) were isolated from human peripheral blood, and demonstrate the interaction of miR-142 and targets (ADAMTS-1) in vitro...
October 2016: European Review for Medical and Pharmacological Sciences
Lindsey L Kennedy, Fanyin Meng, Julie K Venter, Tianhao Zhou, Walker A Karstens, Laura A Hargrove, Nan Wu, Konstantina Kyritsi, John Greene, Pietro Invernizzi, Francesca Bernuzzi, Shannon S Glaser, Heather L Francis, Gianfranco Alpini
Cholestasis is a condition that leads to chronic hepatobiliary inflammation, fibrosis, and eventually cirrhosis. Many microRNAs (miRs) are known to have a role in fibrosis progression; however, the role of miR-21 during cholestasis remains unknown. Therefore, the aim of this study was to elucidate the role of miR-21 during cholestasis-induced biliary hyperplasia and hepatic fibrosis. Wild-type (WT) and miR-21(-/-) mice underwent Sham or bile duct ligation (BDL) for 1 week, before evaluating liver histology, biliary proliferation, hepatic stellate cell (HSC) activation, fibrotic response, and small mothers against decapentaplegic 7 (Smad-7) expression...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mathieu Pecqueux, Isabell Liebetrau, Wiebke Werft, Hendrik Dienemann, Thomas Muley, Joachim Pfannschmidt, Benjamin Müssle, Nuh Rahbari, Sebastian Schölch, Markus W Büchler, Jürgen Weitz, Christoph Reissfelder, Christoph Kahlert
MicroRNAs are small non-coding RNAs with a length of 18-25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations-tumor, associated stroma, and host tissue-can provide new insights into the complex tumor biology of colorectal cancer...
October 21, 2016: International Journal of Molecular Sciences
Chang Youn Lee, Sunhye Shin, Jiyun Lee, Hyang-Hee Seo, Kyu Hee Lim, Hyemin Kim, Jung-Won Choi, Sang Woo Kim, Seahyung Lee, Soyeon Lim, Ki-Chul Hwang
Stem cell therapy using adult stem cells, such as mesenchymal stem cells (MSCs) has produced some promising results in treating the damaged heart. However, the low survival rate of MSCs after transplantation is still one of the crucial factors that limit the therapeutic effect of stem cells. In the damaged heart, oxidative stress due to reactive oxygen species (ROS) production can cause the death of transplanted MSCs. Apoptosis signal-regulating kinase 1 (ASK1) has been implicated in the development of oxidative stress-related pathologic conditions...
October 20, 2016: International Journal of Molecular Sciences
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
T Zhong, Y Men, L Lu, T Geng, J Zhou, A Mitsuhashi, M Shozu, N J Maihle, G G Carmichael, H S Taylor, Y Huang
The molecular mechanisms underlying the antineoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH). Exposing cancer cells to metformin leads to hypermethylation of tumor-promoting pathway genes and concomitant inhibition of cell proliferation. Metformin acts by upregulating microRNA let-7 through AMPK activation, leading to degradation of H19 long noncoding RNA, which normally binds to and inactivates SAHH...
October 24, 2016: Oncogene
Chun Chen, Zenghong Lu, Jie Yang, Weichao Hao, Yujuan Qin, Huiyan Wang, Congying Xie, Raoying Xie
MicroRNAs (miRNAs) may act as either tumor suppressors or oncogenes in various types of cancers. Previous studies have indicated that miR-17-5p is involved in the initiation and development of human tumors. However, its mechanism and function in nasopharyngeal carcinoma (NPC) remain largely unclear. In this study, we evaluated the expression profiles of miR-17-5p and p21 in NPC cell lines and tissues by quantitative real-time PCR (qRT-PCR). For the analysis, we have established a stable overexpression or depletion of miR-17-5p NPC cell lines for analyzing the effects of cell proliferation by MTT, colony formation, and cell cycle assay...
October 24, 2016: Cancer Medicine
Lena Constantin
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules with wide-ranging and subtle effects on protein production. Their activity during the development of the cerebellum provides a valuable exemplar of how non-coding molecules may assist the development and function of the central nervous system and drive neurodevelopmental disorders. Three distinct aspects of miRNA contribution to early cerebellar development will here be reviewed. Aspects are the establishment of the cerebellar anlage, the generation and maturation of at least two principal cell types of the developing cerebellar microcircuit, and the etiology and early progression of autism spectrum disorder...
October 24, 2016: Molecular Neurobiology
Neil M D'Souza, Penny Fang, Jennifer Logan, Jinzhong Yang, Wen Jiang, Jing Li
Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies...
2016: Frontiers in Oncology
Juanjuan Zhao, Chao Chen, Mengmeng Guo, Yijin Tao, PanPan Cui, Ya Zhou, Nalin Qin, Jing Zheng, Jidong Zhang, Lin Xu
Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice...
2016: Frontiers in Immunology
Koichi Wakabayashi, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Shinya Tanaka, Jun Utsumi, Hidenao Sasaki
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. Recently, we have shown that informative miRNA data can be derived from archived formalin-fixed paraffin-embedded (FFPE) samples from postmortem cases of amyotrophic lateral sclerosis and normal controls. miRNA analysis has now been performed on FFPE samples from affected brain regions in patients with multiple system atrophy (MSA) and the same areas in neurologically normal controls. We evaluated 50 samples from patients with MSA (n=13) and controls (n=13)...
October 20, 2016: Neuroscience Letters
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