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Chhaya Sharma, Debasisa Mohanty
LIN28 protein inhibits biogenesis of miRNAs belonging to the let-7 family by binding to precursor forms of miRNAs. Overexpression of LIN28 and low levels of let-7 miRNAs are associated with several forms of cancer cells. We have performed multiple explicit solvent molecular dynamics simulations ranging from 200 to 500 ns in length on different isoforms of preE-let-7 in complex with LIN28 and also in isolation to identify structural features and key specificity-determining residues (SDRs) that are important for the inhibitory role of LIN28...
January 24, 2017: Biochemistry
Nosheen Masood, Azra Yasmin
Involvement of micro RNAs (miRNA) is currently the focus for cancer studies as they effect the post transcriptional expression of different genes. Let-7 family is among the firstly discovered miRNAs that play important role in cell proliferation and dysregulation leading to cell based diseases including cancer. Another family, miRNA-200 prevents transformation of cell to malignant form and tumor formation by interacting with epidermal mesenchymal transition (EMT). Similarly miRNA-125 controls apoptosis and proliferation by affecting multiple genes involved in transcription, immunological defense, resistance against viral and bacterial infections that ultimately leads to cell proliferation, metastasis and finally cancer...
January 9, 2017: Pathology Oncology Research: POR
Hai-Juan Zhu, Zheng-Yi Han, Shu-Fang He, Shi-Yun Jin, Shi-Jin Xu, Xiang-Dong Fang, Ye Zhang
AIMS: Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. The present study aims to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes. MAIN METHODS: Chronic heart failure was established by injecting doxorubicin (2mg/kg/week) for 6weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart...
February 1, 2017: Life Sciences
Lisa Rancan, Carlos Simón, Emmeline Marchal-Duval, Javier Casanova, Sergio Damian Paredes, Alberto Calvo, Cruz García, David Rincón, Agustín Turrero, Ignacio Garutti, Elena Vara
BACKGROUND: Ischemia-reperfusion injury (IRI) is associated with morbidity and mortality. MicroRNAs (miRNAs) have emerged as regulators of IRI, and they are involved in the pathogenesis of organ rejection. Lidocaine has proven anti-inflammatory activity in several tissues but its modulation of miRNAs has not been investigated. This work aims to investigate the involvement of miRNAs in lung IRI in a lung auto-transplantation model and to investigate the effect of lidocaine. METHODS: Three groups (sham, control, and Lidocaine), each comprising 6 pigs, underwent a lung autotransplantation...
December 2016: Anesthesia and Analgesia
Jolana Lipkova, Kamil Duris
BACKGROUND: Stroke is the second leading cause of death worldwide. Understanding of gene expression dynamics could bring new approaches in diagnostics and therapy of stroke. Small noncoding molecules termed "microRNA" represent the most flexible network of gene expression regulators. METHODS: The aim of this review was to briefly describe the structure and function of microRNA and summarize the current knowledge about the involvement of microRNAs in the pathophysiology of ischemic and hemorrhagic stroke based on both experimental and clinical studies...
September 19, 2016: Current Drug Delivery
Farideh Mohammadian, Younes Pilehvar-Soltanahmadi, Faraz Zarghami, Abolfazl Akbarzadeh, Nosratollah Zarghami
Chrysin, as a flavone, has showed cancer chemopreventive activity. The present study utilized the PLGA-PEG-chrysin to evaluate the expression of miR-9 and Let-7a in human gastric cells. The structure of nanoparticles and encapsulated chrysin was evaluated using (1)H NMR, FT-IR, and SEM. MTT assay was used for the evaluation of cytotoxicity effect of nanoencapsulated chrysin. Expression levels of miR-9 and Let7-a were studied by real-time PCR. The results demonstrated that chrysin-PLGA-PEG nanoparticles are more effective than pure chrysin in upregulation of miR-9 and Let-7a due to enhanced uptake by cells...
August 10, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Kai Yao, Suo Qiu, Lin Tian, William D Snider, John G Flannery, David V Schaffer, Bo Chen
In cold-blooded vertebrates such as zebrafish, Müller glial cells (MGs) readily proliferate to replenish lost retinal neurons. In mammals, however, MGs lack regenerative capability as they do not spontaneously re-enter the cell cycle unless the retina is injured. Here, we show that gene transfer of β-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3β stabilizes β-catenin and activates MG proliferation. Downstream of Wnt, β-catenin binds to the Lin28 promoter and activates transcription...
September 27, 2016: Cell Reports
Jing Yu, Ke He, Ting Ren, Yaping Lou, Ayong Zhao
Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development...
July 1, 2016: Physiological Genomics
Domenico Albino, Gianluca Civenni, Cecilia Dallavalle, Martina Roos, Hartmut Jahns, Laura Curti, Simona Rossi, Sandra Pinton, Gioacchino D'Ambrosio, Fausto Sessa, Jonathan Hall, Carlo V Catapano, Giuseppina M Carbone
Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor cells while tending to spare CSC. In seeking to understand mechanisms needed to acquire and maintain a CSC phenotype in prostate cancer, we investigated connections between the ETS transcription factor ESE3/EHF, the Lin28/let-7 microRNA axis, and the CSC subpopulation in this malignancy. In normal cells, we found that ESE3/EHF bound and repressed promoters for the Lin28A and Lin28B genes while activating transcription and maturation of the let-7 microRNAs...
June 15, 2016: Cancer Research
Alexander I Damanakis, Sabine Eckhardt, Annette Wunderlich, Silvia Roth, Thaddeus T Wissniowski, Detlef K Bartsch, Pietro Di Fazio
PURPOSE: Thyroid cancer (TC), the most common endocrine malignancy, increases its incidence worldwide. MicroRNAs have been shown to be abnormally expressed in tumors and could represent valid diagnostic markers for patients affected by TC. Our aim was to analyze the expression of tumorsuppressor hsa-let7b-5p and hsa-let7f-5p, together with their predicted targets SLC5A5 (NIS) and HMGA2, in papillary (PTC), follicular (FTC) and anaplastic (ATC). METHODS: 8 FTC, 14 PTC, 12 ATC and three normal thyroid tissue samples were analyzed for the expression of pre-let7b, hsa-let7b-5p and hsa-let7f-5p as SLC5A5 and HMGA2 by RT-qPCR...
June 2016: Journal of Cancer Research and Clinical Oncology
Andriana G Kotini, Elisa de Stanchina, Maria Themeli, Michel Sadelain, Eirini P Papapetrou
Human pluripotent stem cells (hPSCs) hold great promise for cell therapy. However, a major concern is the risk of tumor formation by residual undifferentiated cells contaminating the hPSC-derived cell product. Suicide genes could safeguard against such adverse events by enabling elimination of cells gone astray, but the efficacy of this approach has not yet been thoroughly tested. Here, we engineered a lentivirally encoded herpes simplex virus thymidine kinase (HSVtk) with expression restricted to undifferentiated hPSCs through regulation by the let7 family of miRNAs...
February 2, 2016: Molecular Therapy. Nucleic Acids
Shaurya Joshi, Jianqin Wei, Nanette H Bishopric
RATIONALE: The let-7 family of microRNAs (miRs) regulates critical cell functions, including survival signaling, differentiation, metabolic control and glucose utilization. These functions may be important during myocardial ischemia. MiR-let-7 expression is under tight temporal and spatial control through multiple redundant mechanisms that may be stage-, isoform- and tissue-specific. OBJECTIVE: To determine the mechanisms and functional consequences of miR-let-7 regulation by hypoxia in the heart...
February 2016: Biochimica et Biophysica Acta
Megumi Yanokura, Kouji Banno, Miho Iida, Haruko Irie, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Eiichiro Tominaga, Daisuke Aoki
Endometrial cancer is a common malignant gynecological tumor, but there are few biomarkers that are useful for early and accurate diagnosis and few treatments other than surgery. However, use of microRNAs (miRNAs) that induces gene downregulation in cells may permit effective and minimally invasive diagnosis and treatment. In endometrial cancer cells, expression levels of miRNAs including miR-185, miR-210 and miR-423 are upregulated and those of miR-let7e, miR-30c and miR-221 are downregulated compared to normal tissues, and these miRNAs are involved in carcinogenesis, invasion and metastasis...
2015: EXCLI journal
Abolfazl Akbari, Mohammad Hossein Ghahremani, Gholam Reza Mobini, Mahdi Abastabar, Javad Akhtari, Manzar Bolhassani, Mansour Heidari
OBJECTIVES: Transforming growth factor-β (TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. MATERIALS AND METHODS: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice...
September 2015: Iranian Journal of Basic Medical Sciences
Maciej Szemraj, Anna Bielecka-Kowalska, Katarzyna Oszajca, Marta Krajewska, Roman Goś, Piotr Jurowski, Michał Kowalski, Janusz Szemraj
BACKGROUND: Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Circulating microRNAs (miRNAs) in serum have emerged as novel candidate biomarkers for many diseases. The aim of the present study was to identify a serum microRNA (miRNA) expression profile specific for dry and wet forms of AMD. MATERIAL AND METHODS: Serum miRNA expression was first screened using TaqMan® Human MicroRNA Array A (Applied Biosystems). An extensive, self-validated, individual, quantitative RT-PCR (qRT-PCR) study was then performed on a cohort of 300 AMD patients (150 wet form and 150 dry form) and 200 controls...
September 14, 2015: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Justin Seltzer, Thomas C Scotton, Keiko Kang, Gabriel Zada, John D Carmichael
INTRODUCTION: Prolactinomas are the most common functional pituitary adenomas. Current classification systems rely on phenotypic elements and have few molecular markers for complementary classification. Treatment protocols for prolactinomas are also devoid of molecular targets, leaving those refractory to standard treatments without many options. METHODS: A systematic literature review was performed utilizing the PRISMA guidelines. We aimed to summarize prior research exploring gene and protein expression in prolactinomas in order to highlight molecular variations associated with tumor development, growth, and prolactin secretion...
February 2016: Pituitary
Bernardo J Krause, Ivo Carrasco-Wong, Angélica Dominguez, Pilar Arnaiz, Marcelo Farías, Salesa Barja, Francisco Mardones, Paola Casanello
BACKGROUND: Growing evidence shows that metabolic syndrome (MetS) is already starting in childhood however there is no consensus regarding how to diagnose this condition in pediatric population. Studies in adults show that altered levels of specific micro-RNAs are related with components of the MetS. OBJECTIVE: We determined the plasma levels of four MetS-associated micro-RNAs (miR-126, miR-132, mir-145 and Let-7e) in 10 to 12 years old children with or without MetS traits...
2015: PloS One
Chian-Shiu Chien, Mong-Lien Wang, Pen-Yuan Chu, Yuh-Lih Chang, Wei-Hsiu Liu, Cheng-Chia Yu, Yuan-Tzu Lan, Pin-I Huang, Yi-Yen Lee, Yi-Wei Chen, Wen-Liang Lo, Shih-Hwa Chiou
Lin28, a key factor for cellular reprogramming and generation of induced pluripotent stem cell (iPSC), makes a critical contribution to tumorigenicity by suppressing Let-7. However, it is unclear whether Lin28 is involved in regulating cancer stem-like cells (CSC), including in oral squamous carcinoma cells (OSCC). In this study, we demonstrate a correlation between high levels of Lin28B, Oct4, and Sox2, and a high percentage of CD44(+)ALDH1(+) CSC in OSCC. Ectopic Lin28B expression in CD44(-)ALDH1(-)/OSCC cells was sufficient to enhance Oct4/Sox2 expression and CSC properties, whereas Let7 co-overexpression effectively reversed these phenomena...
June 15, 2015: Cancer Research
Chong Chen, Fengqi Cao, Lipeng Bai, Yan Liu, Junling Xie, Wei Wang, Qin Si, Jian Yang, Antao Chang, Dong Liu, Dachuan Liu, Tsung-Hsien Chuang, Rong Xiang, Yunping Luo
Considerable evidence suggests that proinflammatory pathways drive self-renewal of cancer stem-like cells (CSC), but the underlying mechanisms remain mainly undefined. Here we report that the let7 repressor LIN28B and its regulator IKBKB (IKKβ) sustain cancer cell stemness by interacting with the Wnt/TCF7L2 (TCF4) signaling pathway to promote cancer progression. We found that LIN28B expression correlated with clinical progression and stemness marker expression in breast cancer patients. Functional studies demonstrated that the stemness properties of LIN28B-expressing human breast and lung cancer cells were enhanced by IKKβ, whereas loss of LIN28B abolished stemness properties in these settings...
April 15, 2015: Cancer Research
Sylvanne M Daniels, Lucile Sinck, Natalie J Ward, Carlos E Melendez-Peña, Robert J Scarborough, Ibrahim Azar, Elodie Rance, Aïcha Daher, Ka-Ming Pang, John J Rossi, Anne Gatignol
Several proteins and RNAs expressed by mammalian viruses have been reported to interfere with RNA interference (RNAi) activity. We investigated the ability of the HIV-1-encoded RNA elements Trans-Activation Response (TAR) and Rev-Response Element (RRE) to alter RNAi. MicroRNA let7-based assays showed that RRE is a potent suppressor of RNAi activity, while TAR displayed moderate RNAi suppression. We demonstrate that RRE binds to TAR-RNA Binding Protein (TRBP), an essential component of the RNA Induced Silencing Complex (RISC)...
2015: RNA Biology
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