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Trends in Cancer Screening: Different Diagnostic Approaches
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
microRNA: Mature microRNAs (miRNA) are derivative of hairpin precursor transcripts. They are short strands of non-coding RNA and extremely conserved. The formation of 21–24 nucleotides are long, double-stranded mature miRNAs that take place in two steps: firstly by the cleavage of primary microRNA (pri-miRNA) with the help of enzyme complex Drosha which takes place inside the nucleus and then through DICER1 in the cytoplasm (Lin and Gregory, 2015). One of the mature miRNA strands, by binding primarily to the 3′untranslated region (UTR) region of mRNA regulates the protein translation process. Moreover, it can repress or activate translational efficacy by binding to the open reading frame (ORF) or 5′UTR of target mRNAs also (Portnoy et al., 2011). miRNAs are known to be involved in a varied range of biological processes such as growth, cell proliferation, body metabolism, and cell signaling (Swanton, 2012). It is noted that miRNAs are stable in the peripheral circulation (Rapisuwon et al., 2016).
From RNA Structures to RNA Nanomachines
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
Sabarinath Jayaseelan, Paul D. Kutscha, Francis Doyle, Scott A. Tenenbaum
The ability for two trans-acting RNAs to structurally interact with each other is an attractive and exciting hypothesis (George and Tenenbaum 2006). Most RNA–RNA interactions are typically visualized as linear base pairing between two sets of sequences or abutting sequences such as kissing complexes. The effect of trans interactions on RNA structure is often not considered. It should not be surprising that eukaryotic cells would have evolved to also use structural changes in RNA (cis as well as trans interactions) to regulate gene expression. Some possible means of interactions are shown in Figure 5.4. The illustration depicts versatility of the miRNA’s control over the message. It can either enhance or reduce protein binding, or in some cases create even alternate binding sites in the same message. The biochemical outcome inside the cell will be different in each case. MicroRNAs and RNA-binding proteins (RBPs) can regulate gene expression, most notably through their actions with the untranslated regions (UTRs) of mRNA. miRNAs modulate RBP-binding sites in a dynamic manner, targeting and sharing a common regulatory code. This would provide a mechanism to influence the structure (shape) of the mRNA to ensure that the appropriate regulatory elements are utilized for the optimal expression of a multifunctional mRNA transcript.
Structures
Published in Thomas M. Nordlund, Peter M. Hoffmann, Quantitative Understanding of Biosystems, 2019
Thomas M. Nordlund, Peter M. Hoffmann
The structure of single-stranded mRNA is illustrated in Figure 5.37. The “structure” in Figure 5.37a shows a block diagram of the contents of the sequence of a typical mRNA in humans. The 5′ cap is a modified guanine nucleotide added to the front (5′) end. This modification allows proper attachment of the mRNA to the ribosome. Coding regions (the codons) are decoded and translated into a protein by the ribosome. Coding regions begin with the “start codon” and end with a “stop codon.” The start codon is usually an AUG triplet and the stop codon is UAA, UAG, or UGA. The coding regions tend to be stabilized by internal base pairs. Untranslated regions (UTRs) are sections of the mRNA that are not translated. These regions are exonic in the mature mRNA. Untranslated regions seem to enhance mRNA stability, localization, and translational efficiency. Some of the elements contained in untranslated regions form a characteristic secondary structure when transcribed into RNA (Figure 5.37b–c). These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element, are targets for proteins to bind. One class of mRNA element, the riboswitches (Figure 5.37b), directly bind small molecules, modifying transcription or translation. The “poly(A) tail” at the 3′ end of mRNA is a long stretch of adenine nucleotides often numbering in the hundreds. This tail promotes transport out of the nucleus and translation. It also helps prevent the mRNA from degrading too soon. The proper picture of mRNA, far from being a long, straight line of nucleotides, is rather a large, three-dimensional macromolecule with active structures designed to interact with proteins in the cell. The tendency of bases to stack and base pair, far from being greatly diminished by the H → OH and T → U changes, is exploited to produce a polymer that is structurally complex and active.
Role of miR-182-5p overexpression in trichloroethylene-induced abnormal cell cycle functions in human HepG2 cells
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Yan Jiang, Zijie Zhou, Ren Fei, Xuan Zhou, Jin Wang, Yizhou Tao, Jianxiang Li, Tao Chen
MicroRNAs (miRNAs) is a class of non-coding single-stranded RNA molecules that regulate target gene expression by binding to the 3ʹ-untranslated region (UTR) of the mRNAs (Hudder and Novak 2008; Wu et al. 2019). miRNAs are involved in various crucial biological processes including regulation of cell differentiation, proliferation, and migration, and are closely associated with tumor development (Chawla et al. 2015; Iorio and Croce 2012; Morishita and Masaki 2015). Previously Jiang et al. (2017a) showed that in mouse BNL CL.2 and Hepa1-6 mouse cells exposed to TCE the expression levels of miR-182-5p were upregulated but the target gene protein and mRNA Cited2 expression levels were downregulated. In order to determine whether human liver cells responded in a similar fashion to mouse, the effect of TCE was examined on cellular processes including proliferation, migration, DNA damage, and apoptosis in human hepatoma cell line HepG2. Further, the expression levels of mir-182-5p and its target gene Cited2 were measured in human normal and liver cancer tissues using Cancer Genome Atlas (TCGA) database.
Effects of radon on miR-34a–induced apoptosis in human bronchial epithelial BEAS-2B cells
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Jing Wu, Bin Sun, Shuyu Zhang, Jie Zhang, Jian Tong, Jihua Nie, Jianxiang Li
MicroRNAs (miRNAs) are small noncoding and high conservation RNAs that bind to the 3ʹ-untranslated region (3ʹUTR) of target mRNA and considered as important post transcriptional regulators in gene expression (Caporali and Costanza 2011). In addition, miRNAs are involved in nearly all fundamental biological processes including metastasis and apoptosis in animals through targeting most of protein coding transcription as reviewed by Ha and Kim. (2014). Tavazoie et al. (2008) reported that miR-126 and miR-335 increased gene expressions suppressed malignant cells metastasis in breast cancer patients. Zhang et al. (2016) found that up-regulation of gene miR-34a enhanced the sensitiviy of cisplatin in gastric cancer cells by inhibiting cell proliferation and apoptosis. Previously Nie et al. (2015) found that miR-34a up-regulation increased apoptosis and reduced migration and invasion in human esophageal squamous cell carcinoma cells. Thus, evidence indicates that in carcinogenesis and apoptosis the involvement of miRNAs play a significant role. However, whether radon exposure affects miR-34a gene regulation and associated apoptosis remains to be determined. Thus, the aim of this study was to investigate whether chronic radon exposure involved miR-34a up-regulation and consequent cellular apoptosis in the observed pulmonary damage using a human bronchial epithelial (BEAS-2B) cell line.
Involvement of MAPK/ERK1/2 pathway in microcystin-induced microfilament reorganization in HL7702 hepatocytes
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Fei Yang, Cong Wen, Shuilin Zheng, Shu Yang, Jihua Chen, Xiangling Feng
MicroRNAs (miRNA) are a class of non-coding RNAs composed of processed products of approximately 22–25 nucleotides in length, which play a key role in down-regulation of target gene expression by imperfectly binding to the 3′-untranslated regions (UTR) of mRNA. miRNA are crucial in cellular processes, such as cell proliferation, cell apoptosis and tumorigenesis and development (Judice et al. 2016). Previously Xu et al. (2012) found in vitro that chronic MC-LR exposure altered miRNA expression profile of hepatic WRL-68 cells and produced phenotypic transformation. Further, Chen et al. (2018) noted that the miRNA expression profile was significantly altered in MC-LR hepatocyte L02 treated cells after 24 hr incubation. In vivo Zhao, Xie, and Fan (2012) performed miRNA microarray analyses in liver tissue after intraperitoneal (ip) injection daily of MC-LR in mice for 28 days. Data demonstrated that the expression levels of several miRNA including miR-34a and miR-21were elevated. These results showed that miRNA are involved in MC-LR-induced hepatic toxicity. However, the mechanisms underlying MC-LR-mediated alterations in miRNA-induced cytoskeletal reorganization remain to be determined.