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Hua Sun, Pora Kim, Peilin Jia, Ae Kyung Park, Han Liang, Zhongming Zhao
Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes...
March 20, 2018: Briefings in Bioinformatics
Yingqi Shao, Sizhou Feng, Jinbo Huang, Jiali Huo, Yahong You, Yizhou Zheng
BACKGROUND: Dyskeratosis congenita (DC) is an inherited telomeropathy characterized by mucocutaneous dysplasia, bone marrow failure, cancer predisposition, and other somatic abnormalities. Cells from patients with DC exhibit short telomere. The genetic basis of the majority of DC cases remains unknown. METHODS: A 2 generational Chinese Han family with DC was studied using targeted capture and next-generation sequencing to identify the underlying DC-related mutations...
March 7, 2018: BMC Medical Genetics
Xiao-Shuai Yuan, Long-Xiang Cao, Ye-Ji Hu, Fei-Chao Bao, Zhi-Tian Wang, Jin-Lin Cao, Ping Yuan, Wang Lv, Jian Hu
Lung cancer, of which non-small cell lung cancer accounts for 80%, remains a leading cause of cancer-related mortality and morbidity worldwide. Our study revealed that the expression of WD repeat containing antisense to P53 (WRAP53) is higher in lung-adenocarcinoma specimens than in specimens from adjacent non-tumor tissues. The prevalence of WRAP53 overexpression was significantly higher in patients with tumor larger than 3.0 cm than in patients with tumor smaller than 3.0 cm. The depletion of WRAP53 inhibits the proliferation of lung-adenocarcinoma A549 and SPC-A-1 cells via G1/S cell-cycle arrest...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Salah Mahmoudi, Sofia Henriksson, Martin Corcoran, Cristina Méndez-Vidal, Klas G Wiman, Marianne Farnebo
No abstract text is available yet for this article.
December 1, 2016: Molecular Cell
Ashish Goyal, Ksenia Myacheva, Matthias Groß, Marcel Klingenberg, Berta Duran Arqué, Sven Diederichs
The CRISPR/Cas9 system provides a revolutionary genome editing tool for all areas of molecular biology. In long non-coding RNA (lncRNA) research, the Cas9 nuclease can delete lncRNA genes or introduce RNA-destabilizing elements into their locus. The nuclease-deficient dCas9 mutant retains its RNA-dependent DNA-binding activity and can modulate gene expression when fused to transcriptional repressor or activator domains. Here, we systematically analyze whether CRISPR approaches are suitable to target lncRNAs...
September 30, 2016: Nucleic Acids Research
H Y Cao, S Wang, Z Y Zhang, J Y Lou
The TP53 5'-untranslated region flanking the gene WRAP53 (also known as WDR79 and TCAB1) has been hypothesized to be associated with cancer risk due to its critical function in regulating p53 levels. In this review, we analyzed the association between the WRAP53 gene rs2287499 C>G polymorphism and risk of cancer using five case-control studies, comprising seven datasets. All analyses were performed using RevMan software. In the overall analysis, no significant association between rs2287499 and risk of cancer was found...
July 25, 2016: Genetics and Molecular Research: GMR
Aaron R Poole, Isioma I Enwerem, Ian A Vicino, Jackson B Coole, Stanley V Smith, Michael D Hebert
Many cellular functions, such as translation, require ribonucleoproteins (RNPs). The biogenesis of RNPs is a multi-step process that, depending on the RNP, can take place in many cellular compartments. Here we examine 2 different RNPs: telomerase and small Cajal body-specific RNPs (scaRNPs). Both of these RNPs are enriched in the Cajal body (CB), which is a subnuclear domain that also has high concentrations of another RNP, small nuclear RNPs (snRNPs). SnRNPs are essential components of the spliceosome, and scaRNPs modify the snRNA component of the snRNP...
October 2, 2016: RNA Biology
C Pederiva, S Böhm, A Julner, M Farnebo
Although evidence that splicing regulates DNA repair is accumulating, the underlying mechanism(s) remain unclear. Here, we report that short-term inhibition of pre-mRNA splicing by spliceosomal inhibitors impairs cellular repair of DNA double-strand breaks. Indeed, interference with splicing as little as 1 h prior to irradiation reduced ubiquitylation of damaged chromatin and impaired recruitment of the repair factors WRAP53β, RNF168, 53BP1, BRCA1 and RAD51 to sites of DNA damage. Consequently, splicing-deficient cells exhibited significant numbers of residual γH2AX foci, as would be expected if DNA repair is defective...
October 2016: Cell Death and Differentiation
H Rassoolzadeh, S Böhm, E Hedström, H Gad, T Helleday, S Henriksson, M Farnebo
Altered expression of the multifunctional protein WRAP53β (WD40 encoding RNA Antisense to p53), which targets repair factors to DNA double-strand breaks and factors involved in telomere elongation to Cajal bodies, is linked to carcinogenesis. While loss of WRAP53β function has been shown to disrupt processes regulated by this protein, the consequences of its overexpression remain unclear. Here we demonstrate that overexpression of WRAP53β disrupts the formation of and impairs the localization of coilin to Cajal bodies...
June 16, 2016: Cell Death & Disease
Aaron R Poole, Michael D Hebert
Telomerase is a ribonucleoprotein comprising telomerase RNA and associated proteins. The formation of the telomerase holoenzyme takes place in the Cajal body (CB), a subnuclear domain that participates in the formation of ribonucleoproteins. CBs also contribute to the delivery of telomerase to telomeres. The protein WRAP53 is enriched within the CB and is instrumental for the targeting of telomerase RNA to CBs. Two other CB proteins, SMN and coilin, are also suspected of taking part in some aspect of telomerase biogenesis...
2016: Biology Open
Jorge Mata-Garrido, Iñigo Casafont, Olga Tapia, Maria T Berciano, Miguel Lafarga
There is growing evidence that defective DNA repair in neurons with accumulation of DNA lesions and loss of genome integrity underlies aging and many neurodegenerative disorders. An important challenge is to understand how neurons can tolerate the accumulation of persistent DNA lesions without triggering the apoptotic pathway. Here we study the impact of the accumulation of unrepaired DNA on the chromatin architecture, kinetics of the DNA damage response and transcriptional activity in rat sensory ganglion neurons exposed to 1-to-3 doses of ionizing radiation (IR)...
April 22, 2016: Acta Neuropathologica Communications
Marwa M Kamel, Marwa Matboli, Maha Sallam, Iman F Montasser, Amr S Saad, Ahmed H F El-Tawdi
There is an increasing interest in using long noncoding RNAs (lncRNAs) as biomarkers in cancer. Predictive biomarkers in hepatocellular carcinoma (HCC) have great benefit in the choice of therapeutic modality for HCC. The aim of this study is to assess lncRNA-urothelial carcinoma associated-1 (lncRNA-UCA1) and WD repeat containing, antisense to TP53 (WRAP53) expression as novel noninvasive biomarkers for diagnosis of HCC in sera of HCC patients compared with chronic hepatitis C virus (HCV) patients and healthy volunteers and to analyze their relationship with respect to the clinicopathologic features...
February 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Laxmi Silwal-Pandit, Hege Russnes, Elin Borgen, Veronica Skarpeteig, Hans Kristian Moen Vollan, Ellen Schlichting, Rolf Kåresen, Bjørn Naume, Anne-Lise Børresen-Dale, Marianne Farnebo, Anita Langerød
WRAP53 protein controls intracellular trafficking of DNA repair proteins, the telomerase enzyme, and splicing factors. Functional loss of the protein has been linked to carcinogenesis, premature aging and neurodegeneration. The aim of this study was to investigate the prognostic significance of WRAP53 protein expression in breast cancer. A tissue microarray was constructed from primary breast tumors and immunostained by a polyclonal WRAP53 antibody to assess the protein expression pattern. Two different patient cohorts with long term follow-up were studied; a test- and a validation set of 154 and 668 breast tumor samples respectively...
2015: PloS One
Mo-Jin Wang, Jie Ping, Yuan Li, Gunnar Adell, Gunnar Arbman, Bjorn Nodin, Wen-Jian Meng, Hong Zhang, Yong-Yang Yu, Cun Wang, Lie Yang, Zong-Guang Zhou, Xiao-Feng Sun
The incidence of colorectal cancer (CRC) in young patients (≤ 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linköping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases...
2015: Scientific Reports
Shan-Shan Yuan, Yi-Dan Lu, Cui-Ling Wu, Hui-Ping Li, Hui Ge, Yu-Ming Zhang
OBJECTIVE: To analyze the clinical features and genotype in a 8-year-old boy with dyskeratosis congenita (DC). METHODS: We reviewed the clinical data of the case and amplified 7 DC-related genes (including DKC1,TERT,TERC,TINF2,NOP10, NHP2 and WRAP53) using polymerase chain reaction for DNA sequence analysis to identify the abnormal exons. RESULTS: DNA sequence analysis showed a c.85-15T>C mutation in DKC1 gene of the patient. His mother was a carrier of the mutated gene and presented with partial clinical features such as abnormal nails...
April 2015: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Isioma I Enwerem, Guowei Wu, Yi Tao Yu, Michael D Hebert
Small nuclear ribonucleoproteins (snRNPs), which are required for pre-mRNA splicing, contain extensively modified snRNA. Small Cajal body-specific ribonucleoproteins (scaRNPs) mediate these modifications. It is unknown how the box C/D class of scaRNPs localizes to Cajal Bodies (CBs). The processing of box C/D scaRNA is also unclear. Here, we explore the processing of box C/D scaRNA 2 and 9 by coilin. We also broaden our investigation to include WRAP53 and SMN, which accumulate in CBs, play a role in RNP biogenesis and associate with coilin...
2015: PloS One
Hui Qiu, De-Ying Zhao, Li-Mei Yuan, Gong Zhang, Cong-Hua Xie
BACKGROUND: Telomere length is closely associated with cellular radiosensitivity and WRAP53 is required for telomere addition by telomerase. In this research we assessed radiosensitivity of laryngeal squamous cell carcinoma Hep-2 cell lines after WRAP53 inhibition, and analyzed the molecular mechanisms. MATERIALS AND METHODS: phWRAP53-siRNA and pNeg-siRNA were constructed and transfected into Hep-2 cells with lipofectamine. Expression of WRAP53 was analyzed by RT-PCR and Western-blottin, radiosensitivity of Hep-2 cells was assessed colony formation assay, and the relative length of telomeres was measured by QPCR...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Sofia Henriksson, Marianne Farnebo
The WRAP53 gene encodes both an antisense transcript (WRAP53α) that stabilizes the tumor suppressor p53 and a protein (WRAP53β) involved in maintenance of Cajal bodies, telomere elongation and DNA repair. WRAP53β is one of many proteins containing WD40 domains, known to mediate a variety of cellular processes. These proteins lack enzymatic activity, acting instead as platforms for the assembly of large complexes of proteins and RNAs thus facilitating their interactions. WRAP53β mediates site-specific interactions between Cajal body factors and DNA repair proteins...
2015: Frontiers in Genetics
Aida Sedaie Bonab, Nasser Pouladi, Mohammad Ali Hosseinpourfeizi, Reyhaneh Ravanbakhsh Gavgani, Roghayeh Dehghan, Parvin Azarfam, Vahid Montazeri, Ashraf Fakhrjou
The WRAP53 (WD40-encoding RNA antisense to p53) gene encodes an antisense RNA, essential for p53 stabilization and induction upon DNA damage. Single nucleotide polymorphisms (SNPs) in WRAP53 have been associated with risk of cancer, which strengthens the role of WRAP53 in the pathogenesis of human malignancies. In fact, WRAP53 has been considered as a candidate cancer susceptibility gene. Accordingly, we performed a study to examine the association of a frequent genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and prognosis among Iranian-Azeri population...
September 2014: Medical Oncology
Chong-kui Sun, Xiao-bo Luo, Ya-ping Gou, Ling Hu, Kun Wang, Chao Li, Zhen-ting Xiang, Ping Zhang, Xiang-li Kong, Chao-liang Zhang, Qin Yang, Jing Li, Li-ying Xiao, Yan Li, Qian-ming Chen
BACKGROUND: WRAP53, including α, β and γ isoforms, plays an important role not only in the stability of p53 mRNA, but also in the assembly and trafficking of the telomerase holoenzyme. It has been considered an oncogene and is thought to promote the survival of cancer cells. The aim of this study was to detect the role of TCAB1 (except WRAP53α) in the occurrence and development of head and neck carcinomas. METHODS: Immunohistochemistry was used to detect the TCAB1 expression in clinical specimen sections and performed western blotting to check the TCAB1 expression levels in cell lines...
2014: Molecular Cancer
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