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Proteins and Proteomics
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
A DNA transcription unit encoding for a protein contains not only the sequence that will eventually be directly translated into the protein but also regulatory sequences that direct and regulate the synthesis of that protein. The regulatory sequence before the coding sequence is called the five-prime untranslated region (5′UTR) and is also known as the upstream process. The sequence following the coding sequence is called the three prime untranslated region (3′UTR) and is also known as the downstream process. Transcription has some proofreading mechanisms, but they are less effective than the controls for copying DNA. Therefore, transcription has a lower copying fidelity than DNA replication. As in DNA replication, DNA is read from 3′—5′ during transcription. Meanwhile, the complementary RNA is created from the 5′—3′ direction. Although DNA is arranged as two antiparallel strands in a double helix, only one of the two DNA strands, called the template strand, is used for transcription. This is because RNA is only single-stranded, as opposed to double-stranded DNA. The other DNA strand is called the coding strand because its sequence is the same as the newly created RNA transcript except for the substitution of uracil for thymine. The use of only the 3′—5′ strand eliminates the need for the Okazaki fragments seen in DNA replication (Figure 3.2).
MicroRNA signaling during regeneration
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Regenerative medicine aims to restore structure and function of damaged organs, to replace dying cells, and to regrow organs and limbs one day. The therapeutic modulation of miRNA expression within a tissue after injury is an interesting and a very attractive clinical strategy within regenerative medicine. MicroRNAs have the capability to simultaneously regulate the expression of dozens to hundreds of gene products by binding, with high specificity, to predictable target sites in the 3′ UTR of a transcript, therefore minimizing the potential for off-target effects. Therefore, development of miRNA-based therapeutic reagents could provide clinically desirable outcomes for regulating the complex reaction of tissues to traumatic injury.
Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Non-coding RNAs (ncRNAs) are an emerging class of epigenetic regulators. MicroRNAs (-22nt) mediate post-transcriptional repression of gene expression via direct interaction with the 3’UTR of its target mRNA sequences. Partial complementary sequences ~2 to 7 bp in length could be sufficient to induce miRNA-induced silencing complex (miRISC)- mediated mRNA degradation. Given the promiscuous nature of microRNAs, up to a third of the transcriptome could be modulated in this manner. Dysregulation of MicroRNAs is commonly observed in human malignancies including lung, gastric, colon, liver, prostate, and breast cancers (Caliv and Croce, 2006). The functional impact of microRNAs is highly variable, and can be either oncogenic or tumor suppressive in a microRNA- and context-dependent manner. MicroRNAs with known oncogenic functions include miR-17, miR-19, miR-21, miR-155, and miR-569 (Zhang et al., 2007), and they all mediate the post-transcriptional silencing of target tumor suppressor genes. MicroRNAs are also putative drug targets in cancer, as their levels can be manipulated by antisense mechanisms or synthetic microRNA mimetics. LncRNAs (>200 nt) encompass a diverse class of lncRNAs that resemble many features of mRNAs but have no coding potential. Emerging work in recent years has led to the characterization of putative lncRNAs associated with carcinogenesis. LncRNAs influence gene expression via several mechanisms, including (1) control of local chromatin structure, (2) recruitment of transcriptional co-activators or co-repressors, (3) interaction with proteins to promote assembly of protein complexes and (4) sequestration of miRNAs. We are just beginning to probe the role of lncRNAs in cancer development and a vast majority of lncRNAs remain to be identified.
Construction of lung cancer serum markers based on ReliefF feature selection
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2023
Yong Li, Nan-Ding Yu, Xiang-Li Ye, Mei-Chen Jiang, Xiang-Qi Chen
MicroRNAs (miRNAs) are a group of small non-coding RNA molecules composed of 20–22 nucleotides, which can directly bind and repress the translation of the 3′-UTR of the target gene mRNA (Du et al. 2021). The minimally invasive nature of liquid biopsy allows sequential sampling and can capture genetic changes of multiple tumors simultaneously, with the convenience that it lacks in tissue biopsy (Adams et al. 2022), liquid biopsy therefore becomes a popular research direction. Blood is one of the ways of liquid biopsy. Wang et al. (2022) incubated the collected serum with iron nanoparticles and used laser desorption/ionization mass spectrometry (LDI-MS) for analysis. Finally, a deep learning method was used to construct an early LUAD diagnostic model based on serum metabolic fingerprints. The model has good diagnostic performance and can better classify pulmonary nodules, which can assist in the diagnosis of LDCT to a certain extent. Literature suggests that miRNAs can be excellent markers for cancer screening, and miRNAs derived from tumors can be found in the serum. The convenience of serum samples makes the development of serum miRNA markers so promising (Peng and Croce 2016). Numerous miRNAs have been identified as markers for early cancer screening, and miRNA diagnostic models (miR-125b-5p, miR-28-5p, and miR-29a-3p) for detecting endometriosis have been developed by Vanhie et al. (2019). The high mortality and heterogeneity made it complicated for the early detection and prevention of ovarian cancer. However, miRNAs in serum can be used as biomarkers to detect ovarian cancer (Ghafouri-Fard et al. 2020). miR-195 presents high expression in breast cancer patients, which correlates with lymph node status and estrogen receptor status, and thus miR-195 may serve as a novel potentially useful breast cancer biomarker (Heneghan et al. 2010). Expression levels of miR10b, miR34a, miR141, and miR155 in the serum of breast cancer patients are all upregulated and associated with tumor progression, so they may become novel diagnostic markers (Roth et al. 2010). miR-32, miR-182, and miR-143 are associated with intestinal type gastric cancer, and miRNAs can be used as diagnostic biomarkers for different subtypes of gastric cancer (Shin and Chu 2014). Aberrant miRNA expression has been found to be closely linked to the cascade of colorectal carcinogenesis, among which miR-17, miR-19a, miR-20a, and miR-223 work as potential biomarkers for colorectal cancer diagnosis (Zekri et al. 2016). These studies stated that the development of miRNA markers was feasible due to the convenience of serum samples.