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Gianmarco Pallavicini, Francesco Sgro, Francesca Garello, Mattia Falcone, Valeria Bitonto, Gaia E Berto, Federico T Bianchi, Marta Gai, Alessandra Ma Chiotto, Miriam Filippi, Juan C Cutrin, Ugo Ala, Enzo Terreno, Emilia Turco, Ferdinando Di Cunto
Medulloblastoma (MB) is the most common malignant brain tumor in children. Current treatment for MB consists of surgery followed by irradiation of the whole neuraxis and high-dose multi-agent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification and validation of novel target molecules capable of contrasting MB growth without disturbing brain development is needed. Citron kinase protein (CITK), encoded by primary microcephaly gene MCPH17, is required for normal proliferation and survival of neural progenitors...
June 19, 2018: Cancer Research
Xiaoqian Wang, Bing Yang, Yuanping She, Yuan Ye
Ovarian cancer is one of the most common gynecologic malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators in cancer development. The current study investigated the role of lncRNA P73 antisense RNA 1T (TP73-AS1) in ovarian cancer. Quantitative real-time polymerase chain reaction determined the expression levels of TP-73AS1, matrix metallopeptidases (MMPs) messenger RNA. Cell proliferative ability, cell invasion, and migration were CCK-8 and colony formation, and transwell invasion and migration assays, respectively...
June 15, 2018: Journal of Cellular Biochemistry
Ilda Patrícia Ribeiro, Francisco Caramelo, Luísa Esteves, Camila Oliveira, Francisco Marques, Leonor Barroso, Joana Barbosa Melo, Isabel Marques Carreira
Purpose: Although oral squamous cell carcinoma (OSCC) presents great mortality and morbidity worldwide, the mechanisms behind its clinical behavior remain unclear. Biomarkers are needed to forecast patients' survival and, among those patients undergoing curative therapy, which are more likely to develop tumor recurrence/metastasis. Demonstrating clinical relevance of these biomarkers could be crucial both for surveillance and in helping to establish adjuvant therapy strategies. We aimed to identify genomic and epigenetic biomarkers of OSCC prognosis as well as to explore a noninvasive strategy to perform its detection...
2018: Journal of Cancer
Shakhawoat Hossain, Hiroaki Iwasa, Aradhan Sarkar, Junichi Maruyama, Kyoko Arimoto-Matsuzaki, Yutaka Hata
RASSF6 is a member of the tumor suppressor Ras-association domain family (RASSF) proteins. RASSF6 is frequently suppressed in human cancers and its low expression is associated with poor prognosis. RASSF6 regulates cell cycle arrest and apoptosis and plays a tumor suppressor role. Mechanistically, RASSF6 blocks MDM2-mediated p53 degradation and enhances p53 expression. However, RASSF6 also induces cell cycle arrest and apoptosis in the p53-negative background, which implies that the tumor suppressor function of RASSF6 does not depend solely on p53...
June 11, 2018: Molecular and Cellular Biology
Guangling Yang, Ruipeng Song, Limin Wang, Xuejian Wu
Long non-coding RNA P73 antisense RNA 1 T (lncRNA TP73-AS1) has been shown to involve in the progression of numerous tumors. Nevertheless, the expression as well as the functional mechanisms of TP73-AS1 in osteosarcoma (OS) are still largely unknown. This study aimed to explore the roles and underlying mechanism of TP73-AS1 in OS progression. In thye present study, TP73-AS1 expression was significantly increased in OS tissues and cell lines. High TP73-AS1 expression was associated with poor overall survival of OS patients...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hua Jiang, Lin Cheng, Pan Hu, Renbin Liu
Breast cancer is the second leading cause of cancer‑associated mortalities in women. Tamoxifen (TAM) is an endocrine therapy commonly used in the treatment of patients with breast cancer expressing estrogen receptor α. However, treatment often ends in failure due to the emergence of drug resistance. MicroRNAs (miRNAs), a family of small non‑coding RNAs, serve critical roles in the regulation of gene expression and cell events. To date, whether miRNA‑663b could mediate TAM resistance in breast cancer remains unknown...
May 23, 2018: Molecular Medicine Reports
Lin Zhang, Fengqi Fang, Xin He
Long noncoding RNAs (lncRNAs) are a type of noncoding RNA transcript that are characterized by lack of protein-coding capacity. The vital role of lncRNAs in non-small cell lung cancer (NSCLC) is attracting increasingly more attention. In the present study, we investigate the role of lncRNA antisense RNA of the TP73 gene (TP73-AS1) in NSCLC carcinogenesis. The results demonstrate that TP73-AS1 is markedly upregulated in NSCLC tissues, and functional experiments revealed that TP73-AS1 is significantly increased in NSCLC tissue and cell lines, indicating a possible oncogenic role...
May 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mina Rahmani, Mehdi Talebi, Majid Farshdousti Hagh, Abbas A Hosseinpour Feizi, Saeed Solali
DNA methylation is a dynamic process influencing gene expression by altering either coding or non-coding loci. Despite advances in treatment of Acute Lymphoblastic Leukemia (ALL); relapse occurs in approximately 20% of patients. Nowadays, epigenetic factors are considered as one of the most effective mechanisms in pathogenesis of malignancies. These factors are reversible elements which can be potentially regarded as therapy targets and disease prognosis. DNA methylation, which primarily serves as transcriptional suppressor, mostly occurs in CpG islands of the gene promoter regions...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xiuyun Li, Xiaoyan Wang, Li Mao, Shuhong Zhao, Haidong Wei
TP73‑AS1, a critical cancer‑associated long noncoding RNA (lncRNA), has been identified in esophageal cancer and glioma. However, its biological role in ovarian cancer (OC) remains to be investigated. The aim of the present study was to investigate the role of TP73‑AS1 in human OC cell lines and clinical tumor samples to determine the function of this molecule. Reverse transcription‑quantitative polymerase chain reaction analysis was carried out to detect that TP73‑AS1 was upregulated in OC tissues and cell lines...
May 3, 2018: Molecular Medicine Reports
Polina Vikhreva, Gerry Melino, Ivano Amelio
p73 (encoded by TP73 gene) is a p53 related protein that functions as a transcriptional factor. Similarly to p53, following DNA damage, p73 is stabilised, activated and controls expression of target genes that are involved in the regulation of cycle arrest and apoptosis. However great complexity to the function of this gene is given by the wide range of its non-tumour related roles, which include neurological development, ciliogenesis and fertility. From the structural point of view, p73 displays an intricate range of regulations because it can be expressed both as a N-terminally deleted dominant-negative isoforms and as multiple alternatively spliced C-terminal isoforms, that can include or not a sterile alfa motif (SAM) domain...
May 4, 2018: Journal of Molecular Biology
Zhiyong Tuo, Jianbin Zhang, Wei Xue
Long noncoding RNAs (lncRNAs) have been identified to have more and more important roles in tumorigenesis and may be novel biomarker for cancer therapy. LncRNA TP73-AS1 is a novel identified lncRNA that has been demonstrated to be increased in several cancers, however, its function in bladder cancer remains unknown. The aim of this work was to examine the expression and role of lncRNA TP73-AS1 in bladder cancer. The expression levels of lncRNA TP73-AS1 in bladder cancer tissues and cell lines were determined by quantitative real-time PCR (qRT-PCR), and its clinical significance was assessed by statistical analysis...
May 23, 2018: Biochemical and Biophysical Research Communications
Subodh Kumar, P Hemachandra Reddy
A non-invasive and early-detectable peripheral biomarker is urgently needed for Alzheimer's disease (AD). The present study is a step forward to verify the biomarker properties of human microRNA-455-3p (Hsa-miR-455-3p) in AD patients. Our previous findings on mild cognitive impaired subjects, AD patients and AD cells and mouse models unveiled the miR-455-3p as a potential peripheral biomarker for AD. In the current study, we verified the differential expression of miR-455-3p in postmortem AD brains obtained from NIH NeuroBioBank, and fibroblasts and B-lymphocytes from both familial and sporadic AD patients from Coriell Cell Repository of National Institutes on Aging...
2018: Frontiers in Aging Neuroscience
Jiyoun Yeo, Diego A Morales, Tian Chen, Erin L Crawford, Xiaolu Zhang, Thomas M Blomquist, Albert M Levin, Pierre P Massion, Douglas A Arenberg, David E Midthun, Peter J Mazzone, Steven D Nathan, Ronald J Wainz, Patrick Nana-Sinkam, Paige F S Willey, Taylor J Arend, Karanbir Padda, Shuhao Qiu, Alexei Federov, Dawn-Alita R Hernandez, Jeffrey R Hammersley, Youngsook Yoon, Fadi Safi, Sadik A Khuder, James C Willey
BACKGROUND: There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis. We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD. METHODS: To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0...
March 5, 2018: BMC Pulmonary Medicine
Anssi Lipponen, Assam El-Osta, Antony Kaspi, Mark Ziemann, Ishant Khurana, Harikrishnan Kn, Vicente Navarro-Ferrandis, Noora Puhakka, Jussi Paananen, Asla Pitkänen
Traumatic brain injury (TBI) induces a wide variety of cellular and molecular changes that can continue for days to weeks to months, leading to functional impairments. Currently, there are no pharmacotherapies in clinical use that favorably modify the post-TBI outcome, due in part to limited understanding of the mechanisms of TBI-induced pathologies. Our system biology analysis tested the hypothesis that chronic transcriptomics changes induced by TBI are controlled by altered DNA-methylation in gene promoter areas or by transcription factors...
February 27, 2018: Acta Neuropathologica Communications
Ilda P Ribeiro, Joana M Rodrigues, Alexandra Mascarenhas, Nadezda Kosyakova, Francisco Caramelo, Thomas Liehr, Joana B Melo, Isabel M Carreira
Oral carcinoma develops from squamous epithelial cells by the acquisition of multiple (epi) genetic alterations that target different genes and molecular pathways. Herein, we performed a comprehensive genomic and epigenetic characterization of the HSC-3 cell line through karyotyping, multicolor fluorescence in situ hybridization, array comparative genomic hybridization, and methylation-specific multiplex ligation-dependent probe amplification. HSC-3 turned out to be a near-triploid cell line with a modal number of 61 chromosomes...
March 24, 2018: Journal of Oral Science
Haiyang Hu, Jian-Mei Liu, Zhenyu Hu, Xi Jiang, Xiaode Yang, Jiangxia Li, Yao Zhang, Haijing Yu, Philipp Khaitovich
MicroRNA (miRNA) sponges are vital components of posttranscriptional gene regulation. Yet, only a limited number of miRNA sponges have been identified. Here, we show that the recently evolved noncoding tumor suppressor transcript, antisense RNA to TP73 gene (TP73-AS1), functions as a natural sponge of human-specific miRNA miR-941. We find unusually nine high-affinity miR-941 binding sites clustering within 1 kb region on TP73-AS1, which forms miR-941 sponge region. This sponge region displays increased sequence constraint only in humans, and its formation can be traced to the tandem expansion of a 71-nt-long sequence containing a single miR-941 binding site in old world monkeys...
May 1, 2018: Molecular Biology and Evolution
Yanqiong Zhang, Funeng Jiang, Huichan He, Jianheng Ye, Xia Mao, Qiuyan Guo, Shu-Lin Wu, Weide Zhong, Chin-Lee Wu, Na Lin
Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA-mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation...
February 21, 2018: Cell Death & Disease
Shuai Xiao, Rensheng Wang, Xiangwei Wu, Wen Liu, Shanshan Ma
P73 antisense RNA 1T (non-protein coding), known as TP73-AS1 or PDAM, is a long noncoding RNA (lncRNA), which may regulate apoptosis by regulation of p53-dependent antiapoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In this study, the effect of TP73-AS1 in human brain glioma cell lines and clinical tumor samples was detected so as to reveal its role and function. In this study, TP73-AS1 was specifically upregulated in brain glioma cell lines and promoted glioma cell growth through targeting miR-124...
February 2018: DNA and Cell Biology
Y Shu, W Ye, Y L Gu, P Sun
OBJECTIVE: This study aimed to investigate the exact role of miR-663b in osteosarcoma (OS) progression and further explore the underlying molecular mechanisms. MATERIALS AND METHODS: The miR-663b expression in human OS cell lines was determined by qRT-PCR, and the results suggested that miR-663b was highly expressed in human OS cells. TargetScan was used to predict the potential targets of miR-663b, and the prediction was confirmed by dual-luciferase reporter assay...
2018: Bratislavské Lekárske Listy
Pierre-Samuel Gillardin, Géraldine Descamps, Sophie Maiga, Benoit Tessoulin, Hanane Djamai, Benedetta Lucani, David Chiron, Philippe Moreau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck, Agnès Moreau-Aubry
(1) Background: TP53 deficiency remains a major adverse event in Multiple Myeloma (MM) despite therapeutic progresses. As it is not possible to target TP53 deficiency with pharmacological agents, we explored the possibility of activating another p53 family member, p73, which has not been well studied in myeloma. (2) Methods: Using human myeloma cell lines (HMCLs) with normal or abnormal TP53 status, we assessed TP73 methylation and expression. (3) Results: Using microarray data, we reported that TP73 is weakly expressed in 47 HMCLs and mostly in TP53 wild type ( TP53wt ) HMCLs ( p = 0...
December 23, 2017: International Journal of Molecular Sciences
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