Journal of nucleic acids investigation最新文献

{"title":"Unusual 5'-regulatory structure and regulation of the murine Mlc1 gene: Lack of promoter-specific functional elements","authors":"D. Henseler, J. D. Turner, M. Eckhardt, M. Mark, Y. Revsin, Michelle K. Lin, T. Kranz, C. Muller, Jobst Meyer","doi":"10.4081/JNAI.2011.2314","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2314","url":null,"abstract":"The MLC1 gene is involved in an autosomal recessive neurological disorder, megalencephalic leucoencephalopathy with subcortical cysts (MLC), which is characterized by macrocephaly during the first year of life and swollen white matter (leucoencephaly). Variants of MLC1 have also been associated with psychiatric disorders such as schizophrenia, major depression and bipolar disorder. Currently, little is known about the encoded protein (MLC1). Judging from its similarity to other known proteins, it may serve as a trans-membrane transporter. However, the function of the encoded protein and its gene regulation has not been investigated successfully so far. We investigated the 5’ region of the murine Mlc1 with respect to regulatory elements for gene expression. A promoter search and an in silico analysis were conducted. Luciferase reporter gene constructs with potential promoter regions were created to study promoter activity in vitro. We found two alternative first exons for the murine Mlc1 but were not able to detect any promoter activity for the investigated reporter gene constructs in different cell lines, thus pointing to the presence of essential cis-acting elements far outside of the region. In silico analysis indicated an uncommon promoter structure for Mlc1, with CCAAT-boxes representing the only noticeable elements.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2011-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70280629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of hpv16 e6 and e7 oncogenic activities by small interference rna induces autophagy and apoptosis in human cervical cancer cells","authors":"Jonathan Salazar-León, Fabiola Reyes-Román, A. Meneses-Acosta, H. Merchant, A. Lagunas-Martínez, Elizabeth Meda-Monzón, M. L. Pita-López, Claudia Gómez-Cerón, V. Bermúdez-Morales, V. Madrid-Marina, O. Peralta-Zaragoza","doi":"10.4081/JNAI.2011.2583","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2583","url":null,"abstract":"Cervical cancer is the second most common form of death by cancer in women worldwide and has special attention for the development of new treatment strategies. Human Papilloma Virus (HPV) persistent infection is the main etiological agent of this neoplasia, and the main cellular transformation mechanism is by disruption of p53 and pRb function by interaction with HPV E6 and E7 oncoproteins. This generates alterations in cellular differentiation and cellular death inhibition. Thus, HPV E6 and E7 oncogenes represent suitable targets for the development of gene therapy strategies against cervical cancer. An attractive technology platform is developing for post-transcriptional selective silencing of gene expression, using small interference RNA. Therefore, in the present study, we used SiHa cells (HPV16+) transiently transfected with specific siRNA expression plasmids for HPV16 E6 and E7 oncogenes. In this model we detected repression of E6 and E7 oncogene and oncoprotein expression, an increase in p53 and hypophosphorylated pRb isoform protein expression, and autophagy and apoptosis morphology features. These findings suggest that selective silencing of HPV16 E6 and E7 oncogenes by siRNAs, has significant biological effects on the survival of human cancer cells and is a potential gene therapy strategy against cervical cancer.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70281188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P53 and microRNAs in chronic lymphocytic leukemia","authors":"J. Bloehdorn, C. Langer, H. Döhner, T. Zenz, S. Stilgenbauer","doi":"10.4081/JNAI.2011.2414","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2414","url":null,"abstract":"There has been considerable progress in characterising chronic lymphocytic leukemia with respect to the underlying biology and the corresponding clinical presentation. Most patients with CLL live for years without the need for therapy. This does not hold true for patients that exhibit inactivation of the tumour suppressor p53 or, possibly, its pathway members. Deletions of chromosome 17p and mutations of TP53 are the main characteristic of aggressive and refractory disease. In this review we will outline the current understanding of mechanisms known to contribute to dysfunctional p53 and its connection to microRNAs.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2011-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70280771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2 splice variants and their relevance in breast cancer","authors":"M. Sasso, F. Bianchi, V. Ciravolo, E. Tagliabue, M. Campiglio","doi":"10.4081/JNAI.2011.2454","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2454","url":null,"abstract":"The HER2 gene amplification occurs in 20-30% of breast cancer and is correlated with a poorer prognosis compared to HER2-negative disease due to increased proliferation and metastatic potential. Two major types of receptor inhibitors have been developed for therapy and one for each categories is currently used in clinic: i) the humanized monoclonal antibody trastuzumab, directed against the HER2 extracellular domain; and ii) the EGFR/HER2 dual tyrosine kinase inhibitor lapatinib. However, patients may develop resistance to drugs and show disease progression . Several resistant mechanisms have been explored and are still under investigation. Here, we focus our attention on the role played by the alternative splicing forms of HER2 in mediating HER2 oncogenic activity and in conditioning the response to HER2 therapies. Three HER2 splice variants have been described so far; the p100 and the herstatin gave raised to two secreted proteins of 100 kd and 68 kd, respectively that act as cell growth inhibitors. Herstatin has been described for its ability to interrupt the constitutive HER2 activation, but also for its capacity to hamper HER2 dimerization with the others HER receptors. Interestingly, herstatin, present as mRNA and protein in non cancerous tissue in areas adjacent to breast carcinoma, is absent as protein in 75% of mammary tumors, which indicates that cancer cells are protected by some intrinsic mechanism against the putative growth-inhibitory effects of this naturally occurring molecule. The third splice form of HER2 gene is the Δ16HER2, encoding for a receptor lacking exon16, whose absence determines a constitutive active dimers with transforming activity in vitro and in vivo. The Δ16HER2 binds to trastuzumab to a less extend, due to conformational changes of the extracellular domain. The Δ16HER2 accounts for almost 9% of the total HER2 transcripts in human breast cancers and, additionally, Δ16HER2 levels are supposed to increase proportionally at the increasing of the HER2 wild-type copy numbers in human primary breast cancers. The availability of a specific assay to determine and quantify the expression levels of this splicing form and the availability of Δ16HER2 transgenic mice models made this variant as the most promising for the development of biodrugs. Finally, HER2 carboxy-terminal fragments (CTFs), generated by alternative initiation of translation, were observed in breast cancer patients. In particular, 611-CTF was described to activate multiple signaling pathways since it is expressed as a constitutively active homodimer. Expression of 611-CTF led to development of aggressive and invasive mammary tumors and it was suggested to be a potent oncogene capable of promoting mammary tumor progression and metastasis.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2011-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70281556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GyrB versus 16s rRna sequencing for the identification of Campylobacter jejuni, Campylobacter coli, and Campylobacter lari","authors":"N. Gunther, Jonnee Almond, Xianghe Yan, D. Needleman","doi":"10.4081/JNAI.2011.2303","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2303","url":null,"abstract":"Species of the genus Campylobacter are responsible for the largest number of bacterial food-borne illness cases occurring yearly in the developed world. The majority of disease is caused by three of the thermotolerant Campylobacter species: Campylobacter jejuni, Campylobacter coli, and Campylobacter lari. An inability to differentiate these three species using the commonly employed 16S rRNA sequencing procedure has led to the development of alternative methods to identify these bacteria. Some of these methods include the utilization of the gyrB gene. A reliable method was developed for the differentiation of C. jejuni, C. coli, and C. lari employing the gyrB gene. It involves amplification and sequencing of a species-variable region of the gene with a single pair of DNA primers. The method works well for the separation and organization of the three Campylobacter strains as well as satisfying the suggested guidelines for sequence based identification for most strains investigated.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2011-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70281045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of microRNAs in solid tumors","authors":"Rie Hamano, H. Ishii, H. Miyata, Y. Doki, M. Mori","doi":"10.4081/JNAI.2011.2164","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2164","url":null,"abstract":"Accumulating experimental evidence indicates that microRNAs play important roles in various biological processes, such as cell differentiation, proliferation, metabolism and apoptosis. In addition, several reports concluded that altered expression of specific microRNA genes contributes to the initiation and progression of cancer. Here, we summarize the current knowledge about aberrant expression of various microRNAs in human solid cancers (e.g., lung, breast, and gastric cancers), their target proteins, and the relationship between their expression and response to chemotherapies. We also review the potential for using microRNAs as biomarkers for the diagnosis and cancer therapy. The development of treatment strategies against human solid cancers based on the profile and/or certain features of microRNAs is promising.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2011-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70280816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs, SNPs and Cancer","authors":"A. Vitale, Huiping Tan, P. Jin","doi":"10.4081/JNAI.2011.2236","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2236","url":null,"abstract":"MiRNAs are probable regulators of cell events such as differentiation, propagation and apoptosis. These cellular phenomena are also associated with benign and malignant tumor cells, therefore, it is presumed that miRNAs act as natural oncogenes or tumor suppressor genes. Whether a particular miRNA serves as either could almost be moot when the additional problems of SNPs enter the fray. A miRNA involved with SNPs (miR-SNPs) on any regulatory level, whether naturally cancerinducing or not, could easily undergo an oncogenic transformation. This work reviews targets of miRNAs and the miRNAs themselves frequently containing SNPs reflecting different risks and markers of cancer with emphasis on familial groups and populations of shared heredity.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"28 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2011-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70280945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNAs and cancer: microRNAs and beyond","authors":"R. Raia, G. Calin","doi":"10.4081/JNAI.2011.E5","DOIUrl":"https://doi.org/10.4081/JNAI.2011.E5","url":null,"abstract":"Non-coding RNAs were previously thought to have little importance because they are not directly translated into a protein like their coding counterparts. However, it was recently found that non-coding RNAs do in fact have a much bigger role than previously thought. They are involved in cancer predisposition, development and progression. MicroRNAs, very short non-coding RNAs, are abnormally expressed in cancer and some harbor mutations that affect expression levels. MicroRNA alterations have been observed in all forms of cancer that have been researched to the current date. MicroRNAs are also located in cancer- associated genomic regions, which have been previously shown to affect gene expression leading to the activation or inhibition of cancer growth. Single-nucleotide polymorphisms within microRNAs can predispose someone to cancer. MicroRNAs have been shown to target both tumor suppressors, inhibiting cancer development, as well as oncogenes, stimulating cancer development. Some microRNAs can switch between these two functions and behave as a tumor suppressor at one time and an oncogene at another time. MicroRNAs can be used for diagnostic purposes as well as prognostic evaluations. Outside of microRNAs, ultraconserved genes, another group of non-coding RNAs, also express differently in cancer patients. Large intervening non-coding RNAs, specifically one termed HOTAIR, have been quantified in very high levels in cancer cells and have been implicated in metastasis. Further research into noncoding RNAs may allow for the development of therapies that will target non-coding RNAs creating better treatment options for cancer patients, improving their prognosis. This review discusses the most current discoveries about non-coding RNAs, revealing their associations with cancer.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"27-30"},"PeriodicalIF":0.0,"publicationDate":"2011-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.E5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70281107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Online resources for microRNA analysis","authors":"P. Alexiou, Manolis Maragkakis, A. Hatzigeorgiou","doi":"10.4081/JNAI.2011.2161","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2161","url":null,"abstract":"The use of online tools for bioinformatics analyses is becoming increasingly widespread. Resources specific to the field of microRNAs are available, varying in scope and usability. Online tools are the most useful for casual as well as power users since they need no installation, are hardware independent and are used mostly through graphic user interfaces and links to external sources. Here, we present an overview of useful online resources that have to do with microRNA genomics, gene finding, target prediction and functional analysis.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2011-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70280757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic implications of microRNAs in human cancer","authors":"M. Rossbach","doi":"10.4081/JNAI.2011.2200","DOIUrl":"https://doi.org/10.4081/JNAI.2011.2200","url":null,"abstract":"MicroRNAs (miRNAs) are a class of highly evolutionarily conserved non-coding RNAs (ncRNAs) that modulate gene expression. Several studies have shown that the expression of miRNAs is deregulated in human malignancies. For ncRNAs and miRNAs, such gene-profiling studies in tumorigenic tissues have identified significant signatures that are of both diagnostic and prognostic value. Addressing the functions of ncRNAs not only give insights into the molecular mechanisms that underlie complex genetic processes, but may also elucidate novel mechanisms that contribute to early stages of tumor development, progression and metastasis. MiRNA-based novel approaches target the ncRNAome, including, for instance, miRNA expression levels and improved designs of miRNA-mimics or more precise target-predictions, prevent off-target effects of novel drugs and make miRNAs become a highly efficient class of therapeutics. For miRNA-based therapeutic studies two direct strategies are currently under investigation, viz. (i) the overexpression of given miRNAs to inhibit the expression of protein-coding genes or (ii) the inhibition of target miRNAs with antisense constructs like antagomiRs. Indirect strategies include the use of novel drugs that modulate miRNA expression levels by directly targeting their processing or transcription. Further, miRNA-based biomarkers have a significant impact on the development of both therapeutic and diagnostic agents, a concept known as theranostics and are highly relevant for drug development and personalized medicine.","PeriodicalId":89421,"journal":{"name":"Journal of nucleic acids investigation","volume":"2 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2011-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4081/JNAI.2011.2200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70280864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}