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Qian Li, Wenying Zhu, Bei Zhang, Yiping Wu, Yufeng Yuan, Haiyan Zhang, Jie Li, Kai Sun, Hua Wang, Tingting Yu
Background: Many long noncoding RNAs (lncRNAs), including lncRNA MALAT1, are involved in various cardiac diseases. We evaluated the effects of tag single nucleotide polymorphisms (tag-SNPs) on MALAT1 gene in a Chinese population of children with congenital heart disease (CHD). Methods:  In the present study, 713 CHD patients and 730 gender- and age-matched newborns without CHD were genotyped for MALAT1 tag-SNPs rs11227209, rs619586, and rs3200401. Further investigation of SNP's function was performed by luciferase assay...
March 20, 2018: Bioscience Reports
Ibrahim O Alanazi, Sami A AlYahya, Esmaeil Ebrahimie, Manijeh Mohammadi-Dehcheshmeh
Exponentially growing scientific knowledge in scientific publications has resulted in the emergence of a new interdisciplinary science of literature mining. In text mining, the machine reads the published literature and transfers the discovered knowledge to mathematical-like formulas. In an integrative approach in this study, we used text mining in combination with network discovery, pathway analysis, and enrichment analysis of genomic regions for better understanding of biomarkers in lung cancer. Particular attention was paid to non-coding biomarkers...
March 16, 2018: Gene
Qiang Hao, Lei He, Jiming Zhou, Yuan Yuan, Xiaowen Ma, Zhijun Pang, Weina Li, Yingqi Zhang, Wei Zhang, Cun Zhang, Meng Li
BACKGROUND: Thymosin beta 4 (Tβ4) is a 43-amino-acid peptide with protective properties in myocardium injury. Previously, we produced a recombinant human dimeric Tβ4 (DTβ4). Here, the cardioprotective effects of DTβ4 and the molecular mechanisms underlying its enhanced activity were investigated. METHODS AND RESULTS: Echocardiography measurements showed that the cardioprotective effect of DTβ4 in myocardial infarction mice was significantly higher than that of wild-type Tβ4...
March 14, 2018: International Journal of Cardiology
Lin Bai, Aihua Wang, Yali Zhang, Xiaofeng Xu, Xiao Zhang
Long non-coding RNAs (lncRNAs) are critical regulators in chemoresistance of various tumors including ovarian cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be upregulated and contributed to ovarian cancer tumorigenesis. The aim of this study was to explore the roles of MALAT1 and the underlying molecular regulatory mechanism in the chemoresistance of ovarian cancer cells. Our data demonstrated that MALAT1 and Notch1 mRNA were upregulated in ovarian cancer tissues, as well as cisplatin (CDDP)-resistant ovarian cancer cells...
March 13, 2018: Experimental Cell Research
Shuping Peng, Lihua Cao, Shiwei He, Yancheng Zhong, Haotian Ma, Yanru Zhang, Cijun Shuai
Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs) and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs) are a family of transcripts longer than 200 nt without or with very low protein-coding potential...
2018: Stem Cells International
Christian L Lino Cardenas, Chase W Kessinger, Yisha Cheng, Carolyn MacDonald, Thomas MacGillivray, Brian Ghoshhajra, Luai Huleihel, Saifar Nuri, Ashish S Yeri, Farouc A Jaffer, Naftali Kaminski, Patrick Ellinor, Neal L Weintraub, Rajeev Malhotra, Eric M Isselbacher, Mark E Lindsay
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1...
March 8, 2018: Nature Communications
S Li, X Liu, H Li, H Pan, A Acharya, Y Deng, Y Yu, R Haak, J Schmidt, G Schmalz, D Ziebolz
BACKGROUND AND OBJECTIVES: Long noncoding RNAs (lncRNAs) play critical and complex roles in regulating various biological processes of periodontitis. This bioinformatic study aims to construct a putative competing endogenous RNA (ceRNA) network by integrating lncRNA, miRNA and mRNA expression, based on high-throughput RNA sequencing and microarray data about periodontitis. MATERIAL AND METHODS: Data from 1 miRNA and 3 mRNA expression profiles were obtained to construct the lncRNA-associated ceRNA network...
March 8, 2018: Journal of Periodontal Research
Qin Chen, Xiaoyan Huang, Renjie Li
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), as a long chain non-coding RNA (lncRNA), has been reported to be upregulated in Parkinson's disease (PD). However, the mechanisms underlying this process remain unknown. Hence, to investigate the role of MALAT1 in PD, N-methyl-4-phenylpyridinium (MPP+ ) was used to induce PD in vitro in the MN9D dopaminergic neuronal cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD in vivo in C57BL/6 mice. Quantitative Real-Time PCR (qRT-PCR) and western blot assay showed that the expression levels of MALAT1 and leucine-rich repeat kinase (LRRK2) were increased, and that of miR-205-5p was decreased in the midbrains of mice in which PD was induced by MPTP...
2018: American Journal of Translational Research
Zhixian Fang, Wenyu Chen, Zuguo Yuan, Xinge Liu, Hao Jiang
Multiple drug resistance is the main reason for chemotherapeutic failure in lung cancer patients with complex molecular mechanisms. LncRNA-MALAT1 plays functional roles in the progression of carcinomas and development of drug resistance. We aimed to identify the role of MALAT1 in DDP-resistant non-small cell lung cancer as well as potential mechanisms. Human lung cancer cell line A549 and the DDP-resistant cell line A549/DDP were used. Cell transfection was performed to establish A549/MALAT1 and A549/DDP/shMALAT1 cells...
March 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nicola Amodio, Maria Angelica Stamato, Giada Juli, Eugenio Morelli, Mariateresa Fulciniti, Martina Manzoni, Elisa Taiana, Luca Agnelli, Maria Eugenia Gallo Cantafio, Enrica Romeo, Lavinia Raimondi, Daniele Caracciolo, Valeria Zuccalà, Marco Rossi, Antonino Neri, Nikhil C Munshi, Pierosandro Tagliaferri, Pierfrancesco Tassone
The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) are still to be investigated. Here, we studied the functional significance and the druggability of the oncogenic lncRNA MALAT1 in MM. Targeting MALAT1 by novel LNA-gapmeR antisense oligonucleotide antagonized MM cell proliferation and triggered apoptosis both in vitro and in vivo in a murine xenograft model of human MM. Of note, antagonism of MALAT1 downmodulated the two major transcriptional activators of proteasome subunit genes, namely NRF1 and NRF2, and resulted in reduced trypsin, chymotrypsin and caspase-like proteasome activities and in accumulation of polyubiquitinated proteins...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Huaqi Wang, Li Wang, Guojun Zhang, Chunya Lu, Heying Chu, Rui Yang, Guoqiang Zhao
In this study, we investigated the mechanism by which lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) mediates cisplatin resistance in lung cancer. Lung cancer patients with high MALAT1 levels were associated with cisplatin resistance and low overall survival. Moreover, cisplatin-resistant A549/DDP cells showed higher MALAT1 expression than cisplatin-sensitive lung cancer cells (A549, H460, H1299 and SPC-A1). Dual luciferase reporter and RNA immunoprecipitation assays showed direct binding of miR-101-3p to MALAT1...
January 26, 2018: Oncotarget
Tao Cai, Yu Liu, Jie Xiao
Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system with highly infiltrative and resistant to chemotherapy. Temozolomide (TMZ) is widely used as the first-line treatment for the therapy of GBM. However, a considerable percentage inherent or acquired resistance in GBM accounts for many treatment failures of the TMZ chemotherapy. Therefore, a deeper understanding of the molecular characteristics underlying TMZ resistance and the identification of novel therapeutic target is urgent...
February 26, 2018: Cancer Medicine
Malte Kölling, Celina Genschel, Tamas Kaucsar, Anika Hübner, Song Rong, Roland Schmitt, Inga Sörensen-Zender, George Haddad, Andreas Kistler, Harald Seeger, Jan T Kielstein, Danilo Fliser, Hermann Haller, Rudolf Wüthrich, Martin Zörnig, Thomas Thum, Johan Lorenzen
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells...
February 21, 2018: Scientific Reports
Jorge Melendez-Zajgla, Gabriela E Mercado-Celis, Javier Gaytan-Cervantes, Amada Torres, Nayeli Belem Gabiño, Martha Zapata-Tarres, Luis Enrique Juarez-Villegas, Pablo Lezama, Vilma Maldonado, Karen Ruiz-Monroy, Elvia Mendoza-Caamal
Ovarian fibrosarcomas are extremely rare tumors with little genomic information available to date. In the present report we present the tumoral exome and transcriptome and the germinal exome of an ovarian fibrosarcoma from a 9-years old child. We found a paucity of mutations (0.77/Mb) and CNV alterations. Of these, the most relevant were a point mutation in the metal-binding site of the microRNA-processing DICER1 enzyme and a frame-shift alteration in the tumor suppressor gene NF1. We validated a germinal truncating mutation in DICER1, which was consistent with a DICER1 Syndrome diagnosis, providing the first example of an ovarian fibrosarcoma as the presenting neoplasia in this syndrome...
February 19, 2018: Scientific Reports
Harshavardhan Janga, Marina Aznaourova, Fabian Boldt, Katrin Damm, Arnold Grünweller, Leon N Schulte
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes...
2018: PloS One
Mei-Hua Bao, Vivian Szeto, Burton B Yang, Shu-Zhen Zhu, Hong-Shuo Sun, Zhong-Ping Feng
Stroke is one of the leading causes of mortality and disability worldwide. Uncovering the cellular and molecular pathophysiological processes in stroke have been a top priority. Long non-coding (lnc) RNAs play critical roles in different kinds of diseases. In recent years, a bulk of aberrantly expressed lncRNAs have been screened out in ischemic stroke patients or ischemia insulted animals using new technologies such as RNA-seq, deep sequencing, and microarrays. Nine specific lncRNAs, antisense non-coding RNA in the INK4 locus (ANRIL), metastasis-associate lung adenocarcinoma transcript 1 (MALAT1), N1LR, maternally expressed gene 3 (MEG3), H19, CaMK2D-associated transcript 1 (C2dat1), Fos downstream transcript (FosDT), small nucleolar RNA host gene 14 (SNHG14), and taurine-upregulated gene 1 (TUG1), were found increased in cerebral ischemic animals and/or oxygen-glucose deprived (OGD) cells...
February 15, 2018: Cell Death & Disease
Sho Ikeda, Akihiro Kitadate, Fumito Abe, Naoto Takahashi, Hiroyuki Tagawa
In multiple myeloma (MM), the bone marrow (BM) microenvironment may contain a myeloma cell fraction that has acquired treatment resistance by undergoing an epigenetic gene expression change. Hypoxic stress is an important factor in the BM microenvironment. Recently, we demonstrated that miR-210 was upregulated in hypoxia and downregulated IRF4, which is known as an essential factor in myeloma oncogenesis in normoxia. In the study, we demonstrated that myeloma cells still showed a strong antiapoptotic phenotype despite IRF4 downregulation, suggesting that another antiapoptotic factor might be involved under hypoxic stress...
February 27, 2018: Blood Advances
Jun Ma, Kaiming Wu, Kuanzhi Liu, Rong Miao
OBJECTIVE: To explore the ability of MALAT1 to influence non-small cell lung cancer (NSCLC) A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy. METHODS: LncRNA MALAT-1 in normal HBE cells and human NSCLC cells was measured. A549 cells were treated with si-MALAT-1, negative control and si-MALAT-1 + rapamycin. The mRNA levels of MALAT-1, P62 and LC3 was determined by the qRT-PCR and the protein levels of autophagy-related proteins by the western blotting...
January 29, 2018: Cancer Biomarkers: Section A of Disease Markers
Jin-Lin Shang, Qing Cheng, Sheng-Jie Duan, Lu Li, Li-Ya Jia
Previous human and animal studies demonstrated that voluntary exercise may improve cognitive function and facilitate neuronal plasticity in ischemia/reperfusion (I/R) models. However, the possible underlying mechanisms remain to be elucidated. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), may be associated with the functions and dysfunctions of endothelial cells. The present study investigated whether spontaneous running‑wheel (RW) exercise‑induced MALAT1 expression changes may be associated with the cognitive improvement of mice following I/R injury...
February 12, 2018: International Journal of Molecular Medicine
Tie-Feng Song, Li-Wen Huang, Ying Yuan, Hui-Qin Wang, Hong-Peng He, Wen-Jian Ma, Li-Hong Huo, Hao Zhou, Nan Wang, Tong-Cun Zhang
Vascular smooth muscle cells (VSMCs), switching from a differentiated to a proliferative phenotype, contribute to various vascular diseases. However, the role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 MALAT1 in the phenotype switching of VSMCs remains unclear. Here, we report that the knockdown of MALAT1 promotes the transformation of smooth muscle cells from a proliferative phenotype to a differentiated phenotype. MALAT1 knockdown inhibited cellular proliferation and migration, leading to significant cell cycle arrest in the G2 phase...
January 12, 2018: Oncotarget
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