Long non-coding RNA in cancer Hauptman, Nina; Glavač, Damjan
International Journal of Molecular Sciences,
02/2013, Letnik:
14, Številka:
3
Journal Article, Book Review
Recenzirano
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Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and ...epigenetic mechanisms of gene regulation. LncRNAs are deregulated in a number of cancers, demonstrating both oncogenic and tumor suppressive roles, thus suggesting their aberrant expression may be a substantial contributor in cancer development. In this review, we will summarize their emerging role in human cancer and discuss their perspectives in diagnostics as potential biomarkers.
Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, ...intracellular trafficking, and chromosome remodeling. Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer. Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice. Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients.
Amyotrophic lateral sclerosis (ALS) is a complex multi-system neurodegenerative disorder with currently limited diagnostic and no therapeutic options. Despite the intense efforts no clinically ...applicable biomarkers for ALS are yet established. Most current research is thus focused, in particular, in identifying potential non-invasive circulating biomarkers for more rapid and accurate diagnosis and monitoring of the disease. In this review, we have focused on messenger RNA (mRNA), non-coding RNAs (lncRNAs), micro RNAs (miRNAs) and circular RNA (circRNAs) as potential biomarkers for ALS in peripheral blood serum, plasma and cells. The most promising miRNAs include miR-206, miR-133b, miR-27a, mi-338-3p, miR-183, miR-451, let-7 and miR-125b. To test clinical potential of this miRNA panel, a useful approach may be to perform such analysis on larger multi-center scale using similar experimental design. However, other types of RNAs (lncRNAs, circRNAs and mRNAs) that, together with miRNAs, represent RNA networks, have not been yet extensively studied in blood samples of patients with ALS. Additional research has to be done in order to find robust circulating biomarkers and therapeutic targets that will distinguish key RNA interactions in specific ALS-types to facilitate diagnosis, predict progression and design therapy.
Summary MicroRNAs are small, noncoding RNAs that regulate gene expression by posttranscriptional regulation of target genes. miR-200 family and miR-205 have been shown experimentally to regulate ...epithelial-mesenchymal transition. As epithelial-mesenchymal transition is the postulated pathogenetic mechanism in spindle cell carcinoma, we analyzed the expression of these microRNAs in spindle cell carcinoma of the head and neck in comparison to conventional squamous cell carcinoma of similar location and stage. We also analyzed the expression of classic and desmosomal cadherins, which are believed to be important targets during epithelial-mesenchymal transition. Forty-five cases of spindle cell carcinoma and 45 cases of squamous cell carcinoma of the head and neck were analyzed using real-time polymerase chain reaction for microRNAs, and immunohistochemistry for classic cadherins (E- and N-cadherins) and desmosomal cadherins. We found a significant down-regulation of the miR-200 family and miR-205 , loss of desmosomal cadherins, and an altered expression of classic cadherins in spindle cell carcinoma in comparison to squamous cell carcinoma. Down-regulation of the miR-200 family and miR-205 strongly supports the postulated role of epithelial-mesenchymal transition in spindle cell carcinoma. These microRNAs act on transcription repressors that were also up-regulated in our cases of spindle cell carcinoma, both on mRNA and on protein levels. The result is not only an altered expression of classic cadherins in adherens junctions but also a complete loss of desmosomal cadherins.
V príspevku so predstavljeni termini v sopomenskih dvojicah in nizih v poimenovalnem sistemu z izhodiščnim terminom celica, ki je iztočnica v Slovenskem medicinskem slovarju. Številni pojmi so ...poimenovani z dvema ali več termini, ki se razlikujejo po prevzetosti prvin, strukturi, tvorjenosti in pomenotvornih lastnostih. Tipološko raznovrstnost izkazujejo tudi sopomenski kratični termini in termini z izlastnoimensko prvino. Ob sopomenskih dvojicah iz prevzetega in neprevzetega termina kot pričakovanem tipu so tudi dvojice iz samo prevzetih ali samo neprevzetih terminov. Dvojic s samo neprevzetimi prvinami je najmanj. Sopomenski nizi so iz po sestavi in izvoru različnih terminov z istimi ali različnimi pomenskosestavinskimi lastnostmi. Po številu podtipov se približujejo sopomenskim dvojicam.
Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that form covalently closed continuous loop structures, lacking the terminal 5′ and 3′ ends. CircRNAs are generated in the process of ...back-splicing and can originate from different genomic regions. Their unique circular structure makes circRNAs more stable than linear RNAs. In addition, they also display insensitivity to ribonuclease activity. Generally, circRNAs function as microRNA (miRNA) sponges and have a regulatory role in transcription and translation. They may be also translated in a cap-independent manner in vivo, to generate specific proteins. In the last decade, next-generation sequencing techniques, especially RNA-seq, have revealed great abundance and also dysregulation of many circRNAs in various diseases, suggesting their involvement in disease development and progression. Regarding their high stability and relatively specific differential expression patterns in tissues and extracellular environment (e.g., body fluids), they are regarded as promising novel biomarkers in cancer. Therefore, we focus this review on describing circRNA biogenesis, function, and involvement in human cancer development and address the potential of circRNAs to be effectively used as novel cancer diagnostic and prognostic biomarkers.
Inflammation and oxidative stress are recognized as important contributors to amyotrophic lateral sclerosis (ALS) disease pathogenesis. Our aim was to evaluate the impact of selected ...single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on ALS susceptibility and modification. One-hundred-and-eighty-five ALS patients and 324 healthy controls were genotyped for nine polymorphisms in seven antioxidant and inflammatory genes using competitive allele-specific PCR. Logistic regression; nonparametric tests and survival analysis were used in the statistical analysis. Investigated polymorphisms were not associated with ALS susceptibility. Carriers of at least one polymorphic
rs4880 T or
rs1071676 C allele more often had bulbar ALS onset (
= 0.036 and
= 0.039; respectively).
rs1071676 was also associated with a higher rate of disease progression (
= 0.015). After adjustment for clinical parameters; carriers of two polymorphic
rs1071676 C alleles had shorter survival (HR = 5.02; 95% CI = 1.92-13.16;
= 0.001); while carriers of at least one polymorphic
rs1001179 T allele had longer survival (HR = 0.68; 95% CI = 0.47-0.99;
= 0.046). Our data suggest that common genetic variants in the antioxidant and inflammatory pathways may modify ALS disease. Such genetic information could support the identification of patients that may be responsive to the immune or antioxidant system-based therapies.
Circular RNAs (circRNAs) are emerging as a novel, yet powerful player in many human diseases. They are involved in several cellular processes and are becoming a noteworthy type of biomarkers. Among ...other functions, circRNAs can serve as RNA sponges or as scaffolds for RNA-binding proteins. Here, we investigated a microarray expression profile of circRNAs in leukocyte samples from ALS patients and age- and sex-matched healthy controls to identify differentially expressed circRNAs. We selected 10 of them for a qPCR validation of expression on a larger set of samples, identification of their associations with clinical parameters, and evaluation of their diagnostic potential. In total, expression of 7/10 circRNAs was significant in a larger cohort of ALS patients, compared with age- and sex-matched healthy controls. Three of them (hsa_circ_0023919, hsa_circ_0063411, and hsa_circ_0088036) showed the same regulation as in microarray results. These three circRNAs also had AUC > 0.95, and sensitivity and specificity for the optimal threshold point > 90%, showing their potential for using them as diagnostic biomarkers.
Leberjeva hereditarna optična nevropatija (LHON) je redka dedna mitohondrijska bolezen, ki povzroča slepoto najpogosteje pri mladih odraslih. Navadno se izrazi kot subakutna, neboleča izguba vida na ...eno oko, ki ji sledi poslabšanje vida drugega očesa v nekaj tednih do mesecih. Bolezen večinoma pušča trajne posledice, le pri nekaterih bolnikih lahko v redkih primerih pride do delnega spontanega izboljšanja vida. Razmerje med moškimi in ženskimi bolniki se ocenjuje na 3 : 1. V zadnjih letih je z razvojem zdravilne učinkovine idebenone možno podporno farmakološko zdravljenje, ki lahko prispeva k delnemu izboljšanju vidne funkcije. Bolezen zaradi svoje redkosti velikokrat ostane ne- ali napačno diagnosticirana. V članku predstavljamo štiri klinične primere bolnikov, pri katerih se je po obsežnem in dolgotrajnem diagnosticiranju izkazalo, da imajo LHON. Od leta 1996 se v Sloveniji vodi baza bolnikov z redkimi dednimi očesnimi boleznimi. Na tej podlagi je ocenjena prevalenca LHON 1/72.000. Ob sumu na bolezen so ključni družinska anamneza slabovidnosti po materini strani, genetsko testiranje in napotitev na obravnavo ter zdravljenje v terciarno ustanovo.
The Role of Vitamin A in Retinal Diseases Sajovic, Jana; Meglič, Andrej; Glavač, Damjan ...
International journal of molecular sciences,
01/2022, Letnik:
23, Številka:
3
Journal Article
Recenzirano
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Vitamin A is an essential fat-soluble vitamin that occurs in various chemical forms. It is essential for several physiological processes. Either hyper- or hypovitaminosis can be harmful. One of the ...most important vitamin A functions is its involvement in visual phototransduction, where it serves as the crucial part of photopigment, the first molecule in the process of transforming photons of light into electrical signals. In this process, large quantities of vitamin A in the form of 11-
-retinal are being isomerized to all-
-retinal and then quickly recycled back to 11-
-retinal. Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle). Any fault in the machinery may not only reduce the efficiency of visual detection but also cause the accumulation of toxic chemicals in the retina. This review provides a comprehensive overview of diseases that are directly or indirectly connected with vitamin A pathways in the retina. It includes the pathophysiological background and clinical presentation of each disease and summarizes the already existing therapeutic and prospective interventions.
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