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The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The other epigenetic mechanism is based on noncoding RNA (ncRNA), which is an RNA molecule not translated into a protein but instead used for epigenetic control purposes within a cell. Epigenetic-related ncRNAs include microRNAs (miRNAs), short interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs). In general, ncRNAs regulate gene expression at both the transcriptional and post-transcriptional level. One of the main groups of ncRNAs involved in epigenetic processes is the miRNAs, which predominantly regulate cell cycle, including the processes of proliferation, differentiation and apoptosis. As shown in many studies, miRNAs are thought to be critical for maintaining global gene expression patterns, and they can be controlled through epigenetic mechanisms (Figure 11.17). ncRNAs can also modulate epigenetic mechanisms indirectly within cells by targeting the expression of enzymes responsible for DNA methylation or histone modification.
Epigenetic Reprogramming of Mammalian Primordial Germ Cells
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
Sebastian Canovas, Susana M. Chuva de Sousa Lopes
The re-establishment of 5mC in PGCs requires the de novo DNA methylation machinery, including DNMT3A and DNMT3B. However, both PIWIL and piwi-interacting RNAs (piRNAs) have also been also involved in the de novo methylation of transposable elements and have recently been characterized in human germ cells at different developmental stages and time points during gestation (50,51).
The Indispensable Soma Hypothesis in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
piRNAs (PIWI-Interacting RNAs) are noncoding RNAs but distinct from microRNAs in some characteristics. They are involved in gene silencing of transposons among others, so they protect the germline. These are also expressed in tumor cells and in certain somatic cells which exhibit biological immortality, such as those in hydra. It is well known that genomic instability in somatic cells increases with age. Evidence indicates that the disintegration of somatic genomes (progressive chromatin decondensation for instance) is accompanied by the mobilization of transposable elements (TEs) which can be mutagenic. However, since TEs are silenced in the germline, there is less risk of adverse mutations [105].
Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers
Published in Journal of Extracellular Vesicles, 2019
Isaac Kirubakaran Sundar, Dongmei Li, Irfan Rahman
Transfer RNAs (tRNAs) play an essential role in protein synthesis. There are two main types of tRNA-derived small RNAs (tsRNAs): tRNA-derived fragments (tRFs: 14–30 nucleotides long) and tRNA halves (31–40 nucleotides long). Recent studies have demonstrated that tsRNAs perform several biological functions such as acting as signalling molecules during stress responses, and serving as regulators of transcription, translation, DNA damage response, viral infections, cancer and neurodegeneration [15]. Furthermore, Piwi-interacting RNAs (piRNAs: 36–32 nucleotides long) have been shown to modulate gene expression pathways via interacting with Piwi proteins [16]. Prior studies on differentially expressed piRNAs were reported in several types of malignancies (lung, breast, gastric and colorectal cancers) [16]. However, to date, no study has been conducted to comprehensively analyze different types of small RNA species such as miRNAs, tRNAs and piRNAs in human plasma-derived EVs as circulating biomarkers in smokers and patients with COPD compared to non-smokers by small RNA-sequencing.
Genetic testing for high-grade osteosarcoma: a guide for future tailored treatments?
Published in Expert Review of Molecular Diagnostics, 2018
Claudia Maria Hattinger, Maria Pia Patrizio, Elisa Tavanti, Silvia Luppi, Federica Magagnoli, Piero Picci, Massimo Serra
Non-coding RNAs include a large number of RNA subclasses, mainly involved in the regulation of gene expression. According to their transcript length, non-coding RNAs can be distinguished in small non-coding RNAs (maximum length of 200 base pairs), long non-coding RNAs (lncRNAs, with length greater than 200 base pairs), and circular RNAs (small closed circular RNAs). The group of small non-coding RNAs includes microRNAs (miRNAs), small interfering RNAs (siRNAs), piwi-interacting RNAs, transfer RNAs, and some ribosomal RNAs. In this review, we provide a summary of the miRNAs and lncRNAs that have been studied in clinical samples and which have more consistently suggested to play a role in HGOS tumorigenesis, invasion and metastatic progression, apoptosis and/or chemoresistance. Genes and pathways regulated by miRNAs, which have been described only in HGOS experimental models, were not specifically discussed.
The potential of circulating cell-free RNA as a cancer biomarker: challenges and opportunities
Published in Expert Review of Molecular Diagnostics, 2018
Ivan A. Zaporozhchenko, Anastasia A. Ponomaryova, Elena Yu Rykova, Pavel P. Laktionov
PIWI-interacting RNAs (piRNAs) are another class of short noncoding RNAs, associated with proteins from the distinct PIWI clade of the Argonaute family. These RNAs regulate gene expression at transcriptional and posttranscriptional levels, participate in transposon silencing, protect the integrity of the genomes of the germline cells, and regulate developmental timing [94]. However, more recently, they were also found to be expressed in somatic tissues, such as lung, liver, kidney, brain, and others, and aberrant piRNA expression has been linked to cancer progression and development [95,96]. Subsequently, significant amounts of piRNAs have been discovered in biological fluids, and some of them are reportedly associated with membrane vesicles [76]. Circulating piRNAs have only just came into focus as potential cancer biomarkers, but several candidates for further testing have already been identified, including piR-019825 for colorectal cancer, piR-001311 and piR-016658 in pancreatic cancer, and piR-016658 and piR-020496 in prostate cancer [76]. Further investigation of these RNAs may uncover more potential biomarkers.