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Regulation of Airway Smooth Muscle Proliferation by β2-Adrenoceptor Agonists
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Alastair G. Stewart, Paul R. Tomlinson, Leslie Schachte
E2F transcriptional activity appears to mediate the transition from G1 to S, as the introduction of E2F releases cells from arrest of the cell cycle induced by Rb.189 Furthermore, E2F microinjection also induces DNA synthesis in quiescent fibroblasts.190 However, E2F does not induce malignant transformation of rat embryo fibroblasts in cooperation with activated Ras, a common assay for characterisation of proto-oncogenic properties of genes.191,192 This lack of proto-oncogenic property may be explained by the ability of E2F to induce apoptosis.193 Several genes have been confirmed to have E2F sites within their promoter regions: p34cdc2, cyclin A, c-Myc, B-Myb, Rb, E2F and DHFR.183,184
Synthetic DNA-Based Compounds for the Prevention of Coronary Restenosis: Current Status and Future Challenges
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Andrew Zalewski, Yi Shi, John D. Mannion, Femando Roqué
The transcriptional factor E2F binds to double stranded DNA containing an 8 bp consensus sequence, which results in the activation of cell cycle regulating genes (c-myc, c-myb, cdc2, PCNA). An interesting approach of using double-stranded phosphorothioate oligomers containing the 8 bp cis element (E2F decoy) has been used to inhibit coordinated stimulation of several growth stimulatory genes and prevent neointimal formation in the rat model (Morishita et al., 1995). This is particularly interesting, since it represents a novel application of synthetic DNA (double-stranded decoy oligomer) targeting a key transcriptional factor, as opposed to interacting with a single cell cycle regulating gene.
MicroRNAs in Human Cancers
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Single cistronic miR-17-92 cluster containing six miRNAs (miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92-g1) is located within 800 base pairs in the noncoding gene C13orf25 at 13q31.3 [64]. This region is frequently amplified in follicular lymphoma and diffuse large B cell lymphoma. In addition to being key players in lung development and in regulation of the immune and hematopoietic systems, members of the miR-17-92 cluster are highly expressed in a variety of solid tumors and hematological malignancies, including cancers of the breast, colon, lung, pancreas, prostate, and stomach as well as lymphomas [64]. These miRNAs promote proliferation, inhibit apoptosis, induce tumor angiogenesis, and cooperate with c-myc to cause lymphoma in mice [65]. Interestingly, the miR-17-92 cluster is transactivated by c-myc, an oncogene that is frequently activated in cancer [66]. The effects of this cluster’s expression on cell cycle and proliferation are partly due to its regulation of E2F transcription factors, which are critical regulators of the cell cycle [67]. Conversely, both E2F1 and E2F3 were shown to activate the miR-17-92 cluster, establishing a regulatory loop [68, 69]. These oncogenic miRNAs have been studied as promising therapeutic targets, since their downregulation or knock-down have been demonstrated to induce apoptosis, cell cycle arrest, and inhibition of invasion and metastasis of cancer cells.
ADP Ribosylation Factor 6 Relieves Airway Inflammation and Remodeling by Inhibiting Ovalbumin Induced-Epithelial Mesenchymal Transition in Experimental Asthma, Possibly by Regulating of E2F Transcription Factor 8
Published in Immunological Investigations, 2023
Dongdong Dou, Meirong Bi, Xiuyun Li, Nan Zhang, Mi Xu, Aili Guo, Feng Li, Weiwei Zhu
E2F is a group of genes encoding a family of transcription factors and they form a core transcriptional axis crucial for coordinating the cell cycle (Lammens et al. 2009; Logan et al. 2005). E2F transcription factor 8 (E2F8) is a recently identified atypical member of the E2F family and regulates the cell cycle, polyploidization, angiogenesis and lymphangiogenesis (Lv et al. 2017). In addition, most studies have indicated that E2F8 not only function as an oncogene, in hepatocellular (Deng et al. 2010), lung (Park et al. 2015), and breast cancers (Ye et al. 2016), but is also related to other disease processes including obesity and hepatic steatosis (Shimada et al. 2015; Suwa et al. 2010). However, the involvement and biological function of E2F8 in childhood asthma have not yet been explored. Using bioinformatics, we identified a potential E2F8 binding site in the ARF6 promoter region. Therefore, we hypothesized thatARF6 may be involved in the development of childhood asthma by regulating airway remodeling and inflammation, which may be modulated by E2F8. We proposed to establish an OVA-induced neonatal mouse asthma model using the ARF6 inhibitor SecinH3 to investigate the role of ARF6 in childhood asthma.
Immunology of HPV-mediated cervical cancer: current understanding
Published in International Reviews of Immunology, 2021
Babban Jee, Renu Yadav, Sangeeta Pankaj, Shivendra Kumar Shahi
The viral E6 and E7 proteins play central role in successful pathogenesis of HPV and development of cervix carcinoma as these two proteins encoded by the HPV genome subvert the cell cycle regulatory cascades of the host by binding and degrading the two tumor suppressor proteins p53 and pRB, cell cyclins and cyclin-dependent kinases [30] (Figure 2). By binding to the p53 tumor suppressor protein, HPV E6 protein causes its rapid degradation via an ubiquitin ligase. As a result, the major functions of p53 including G1 arrest, apoptosis and DNA repair are impaired. Since low-risk HPV E6 proteins are not able to bind with p53 tumor suppressor, hence, not causing serious consequence in the cancer progression as like high-risk types [31]. The HPV E7 protein binds to hypophosphorylated form of the retinoblastoma gene product, pRb. This binding disrupts the integrity of the complex between pRb and E2F-1, resulting in the release of E2F-1. After the liberation, E2F-1 facilitates the synthesis of those proteins which are needed by the cell to enter cell cycle’s S phase. As a consequence of inactivation of the p53 and pRB, the genomic instability and uninterrupted proliferation of cells occurs leading to the progression of malignancy [32].
Identification of key genes, regulatory factors, and drug target genes of recurrent implantation failure (RIF)
Published in Gynecological Endocrinology, 2020
Increasing evidence has suggested that abnormal regulation of miRNAs and TFs would lead to diseases. In this study, E2F4 and SIN3A were considered as the key TFs involved in the RIF. The E2F family plays a crucial role on the suppression of proliferation-related genes, and the mutation or highly expression of E2F may be associated with cancers [30]. Zhu et al. reported that down regulated SIN3A caused the loss of embryonic stem cell self-renewal and skewed differentiation into mesendoderm lineage [31]. Loss of SIN3A subunit induced the aberrant methylation of part of the gene promoters and resulted in embryonic lethality in mouse [32]. The present study showed that miRNA-TF-DEGs network also included many miRNAs. miRNA489 and its targets were mainly involved in various of cancer or cancer therapy [33,34]. miRNA199A was dramatically down-regulated in endometriosis patients who would undergo the IF [35]. While, at present, there were few research and reports on the miRNA369-3P, miRNA 422 and miRNA522.