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Molecular Biology and Gene Therapy
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Small interfering RNAs (siRNAs; double stranded) and microRNAs (miRs; single stranded) are biologically significant post-transcriptional regulators of gene expression. siRNAs and miRs are non-coding RNA molecules that base pair with mRNA via the RISC complex, preventing their translation into proteins. In addition, long non-coding RNAs (ncRNAs) have been identified that are thought to regulate various aspects of gene expression and they have been implicated in a number of diseases, including aging and cancer.
Epigenetic Alterations in Alzheimer’s Disease and Its Therapeutic and Dietary Interventions
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
P. M. Aswathy, C. M. Shafeeque, Moinak Banerjee
The majority of the eukaryotic genome is transcribed into non-coding RNAs (ncRNAs), and only ~2% is translated. Non-coding RNAs are mainly classified into two types, based on their size, namely small RNAs (sRNAs) (<200 nucleotides) and long non-coding RNAs (lncRNAs) (>200 nucleotides). ncRNAs play crucial roles in the regulation of most epigenetic mechanisms. The small ncRNAs are involved in silencing of transposable elements (Lisch 2012), miRNAs are involved in gene expression control, lncRNAs in X-chromosome inactivation and DNA imprinting (Jeon et al. 2012), and so on. Moreover, these ncRNAs can also regulate DNA methylation and histone modifications. Thus, ncRNAs are directly and/or indirectly implicated in epigenetic mechanisms.
Radiogenomics
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
The genomics strategy depends on what type of molecular data are available. As mentioned in the introduction, we define radiogenomics as the linking of at least one genome-wide molecular data source with quantitative imaging. The first examples in radiogenomics made use of gene expression data [19,32] initially generated by microarray technology, but now superseded by RNA sequencing technology. Gene expression data provide the easiest and cheapest way to get a snapshot of the molecular processes ongoing in the cell. One can get an idea of the activity of all the processes that are relevant for a particular disease, from single genes such as drug targets, to pathways such as the hallmarks of cancer [33]. However, one challenge is the high dimensionality of gene expression data. In the past in the case of microarray technology [34], one would get activity values for all known genes in the human genomes. However, with the use of RNA sequencing technology, one can get activity values for known and unknown entities and not only protein coding genes. For example, long non-coding RNAs can also be investigated [35].
LncTUG1 ameliorates renal tubular fibrosis in experimental diabetic nephropathy through the miR-145-5p/dual-specificity phosphatase 6 axis
Published in Renal Failure, 2023
Taoxia Wang, Shubei Cui, Xiaoli Liu, Li Han, Xiaoting Duan, Shuning Feng, Sen Zhang, Guiying Li
Long non-coding RNA (LncRNA) has almost no protein-coding ability but has a wide range of biological functions. As an evolutionarily conserved Inc RNA, TUG1 could regulate mitochondrial bioenergy in DN [27]. The study also found that the expression of TUG1 in the podocytes of diabetic mice decreased significantly while upregulating TUG1 could improve mitochondrial function and improve DN podocyte injury. TUG1 is also a regulator of lung fibrosis caused by hypoxia, and an important regulator of cardiac fibroblast-myofibroblast transformation [28]. In the current study, by in vitro study, we confirmed that over expression of TUG1 could significantly reduce the Collagen IV and fibronectin expression in HG-treated HK2 cells; Meanwhile, by AAV-TUG1 lentivirus vector delivery, we also confirm that exogenous TUG1 administration also significantly improve the renal function and ameliorate the interstitial fibrosis in DN mice. All these results prove that TUG1 has satisfactory renal protective effect.
Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors
Published in Annals of Medicine, 2023
Moustafa M. Madkour, Wafaa S. Ramadan, Ekram Saleh, Raafat El-Awady
Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides aberrantly expressed in human cells and play crucial roles in gene regulation. The most well-studied example of lncRNAs is the lncRNA activated by DNA damage (NORAD), which is required for maintaining genome stability. NORAD interacts with RBMX, a component of the DNA-damage response, and promotes the assembly of a ribonucleoprotein complex known as NORAD-activated ribonucleoprotein complex 1 (NARC1). NARC1 complex contains some proteins, including Top I, which are known to enhance genomic stability [128]. In colorectal cancer cells, the knockdown of either RBMX or NORAD increased the incidence of chromosomal segregation errors, decreased replication-fork velocity, and disrupted cell-cycle progression (Figure 4(C)). These events represent phenotypes that are linked to Top I function and could influence the response to its inhibitors [128,129]. Another lncRNA involved in the maintenance of genome integrity is SCAT7 (ELF3-AS1). SCAT7 is essential for cell survival and is increased upon exposure to DNA-damaging drugs such as CPT. Additionally, SCAT7 participates in the proteasome-mediated degradation of Top I and its absence leads to the persistence of TOP1cc that interfere with replication fork progression, resulting in significant intrinsic DNA damage (Figure 4(C)). Therefore, SCAT7 operates as a Top I scaffold by interacting with it and regulating its turnover via a ubiquitin-dependent proteasome pathway. Thus, SCAT7 can be utilized as a predictive biomarker for response to Top I inhibitors [130].
Genetic risk and gastric cancer: polygenic risk scores in population-based case-control study
Published in Expert Review of Molecular Diagnostics, 2023
Fujiao Duan, Ling Liu, Xiaolin Chen, Qian Yang, Yiran Wang, Yaodong Zhang, Kaijuan Wang
Long non-coding RNAs (lncRNAs) have been found to have important functions in the occurrence and development of cancer. Gao et al. found that SNPs in lncRNAs regulatory elements could affect the binding of miRNA to lncRNAs. Therefore, this represents another mechanism by which SNPs regulate the transcription of lncRNAs [22]. Meanwhile, studies have confirmed that lncRNA SNPs were associated with gastric cancer. At the early stage of our series of studies, we screened functional lncRNA SNPs related to gastric cancer through bioinformatics methods, and constructed PRS after genetic association verification. The results showed that PRSs based on lncRNA SNPs can identify individuals at high risk of gastric cancer, and combining with risk factors can improve the stratification [23]. However, it was not found that the lncRNA SNPs data set was included as an independent risk factor in the existing risk prediction models [24–26].