{"title":"Oncolytic Zika Virus: New Option for Glioblastoma Treatment.","authors":"Chao Zhou, Qi Chen, Yun Chen, Cheng-Feng Qin","doi":"10.1089/dna.2022.0375","DOIUrl":"https://doi.org/10.1089/dna.2022.0375","url":null,"abstract":"<p><p>Glioblastoma (GBM) is one of the most aggressive brain tumors and has a high recurrence rate, and effective treatment is urgently needed. GBM stem cells (GSCs) contribute to GBM recurrence as well as therapeutic resistance to radiation and chemotherapy. Several oncolytic viruses (OVs) have been developed and validated in clinical trials with favorable safety profiles and efficacy against GBM. Recently, Zika virus (ZIKV), a mosquito-borne flavivirus, was shown to preferentially target and kill GSCs and showed promising therapeutic effects in treating GBM in preclinical models. In this review, we summarize the known OVs for the treatment of GBM and highlight the major advantages and existing challenges for the clinical development of oncolytic ZIKV.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"267-273"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9569708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Xiao, Dan Wang, Yingda Sheng, Jing Huang, Xiaoqin Ha
{"title":"MicroRNA-126 Regulates Thrombosis Through Endothelial Progenitor Cells.","authors":"Qian Xiao, Dan Wang, Yingda Sheng, Jing Huang, Xiaoqin Ha","doi":"10.1089/dna.2022.0643","DOIUrl":"https://doi.org/10.1089/dna.2022.0643","url":null,"abstract":"<p><p>Thrombosis is a common problem with potentially severe consequences. Endothelial progenitor cells (EPCs) show great potential as a thrombosis therapy due to their angiogenesis-promoting, thrombus-relieving, and anticoagulant functions. However, cell therapies present more clinical challenges than small molecule solutions. MicroRNAs (miRNAs) are small noncoding single-stranded RNAs with wide-ranging regulatory activities. miRNA-126 is highly enriched in EPCs and endothelial cells. Although increasing research showed that mircoRNA-126 (miR-126) can regulate EPC functions through various pathways and cytokines, summaries of these interactions are rare. Therefore, this brief review of recent findings on the relationship between miRNA-126 and EPC function will attempt to clarify the role of miR-126 in thrombosis through regulation of EPCs, with the goal of exploring alternative therapies for thrombotic diseases.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"315-321"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9571154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Virus-Induced Lysis of Tumor and Other Pathogenic Unicellular Entities and Its Potential to Treat Leishmaniasis.","authors":"Janaina Fernandes","doi":"10.1089/dna.2023.0048","DOIUrl":"https://doi.org/10.1089/dna.2023.0048","url":null,"abstract":"<p><p>This article is focused on the main pathways used by viruses to achieve infection and lysis of unicellular eukaryotes described as pathogenic for multicellular organisms. In light of the recent discussions on how tumor cells exhibit unicellular behavior, highly malignant cells can be considered as another unicellular pathogenic entity, but with endogenous origin. Thus, a comparative panel of viral lysis of exogenous pathogenic unicellular eukaryotes such as <i>Acanthamoeba sp.</i>, yeast, and tumors is presented. The important intracellular parasite <i>Leishmania sp</i> is also presented, which, in contrast, has its virulence improved by viral infections. The possible exploitation of viral-mediated eukaryotic cell lysis to overcome infections of <i>Leishmania sp</i> is discussed.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"305-314"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oncolytic Reoviruses: Can These Emerging Zoonotic Reoviruses Be Tamed and Utilized?","authors":"Zhen Yun Siew, Alson Loh, Sharrada Segeran, Pooi Pooi Leong, Kenny Voon","doi":"10.1089/dna.2022.0561","DOIUrl":"https://doi.org/10.1089/dna.2022.0561","url":null,"abstract":"<p><p>Orthoreovirus is a nonenveloped double-stranded RNA virus under the <i>Reoviridae</i> family. This group of viruses, especially <i>mammalian orthoreovirus</i> (MRV), are reported with great therapeutic values due to their oncolytic effects. In this review, the life cycle and oncolytic effect of MRV and a few emerging reoviruses were summarized. This article also highlights the challenges and strategies of utilizing MRV and the emerging reoviruses, avian orthoreovirus (ARV) and pteropine orthoreovirus (PRV), as oncolytic viruses (OVs). Besides, the emergence of potential ARV and PRV as OVs were discussed in comparison to MRV. Finally, the risk of reovirus as zoonosis or reverse zoonosis (zooanthroponosis) were debated, and concerns were raised in this article, which warrant continue surveillance of reovirus (MRV, ARV, and PRV) in animals, humans, and the environment.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"289-304"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Yang, Wensheng Sun, Tao Bi, Jiahao Sun, Zhihua Lu, Jie Li, Honglong Wei
{"title":"ZNF8-miR-552-5p Axis Modulates ACSL4-Mediated Ferroptosis in Hepatocellular Carcinoma.","authors":"Hao Yang, Wensheng Sun, Tao Bi, Jiahao Sun, Zhihua Lu, Jie Li, Honglong Wei","doi":"10.1089/dna.2022.0582","DOIUrl":"https://doi.org/10.1089/dna.2022.0582","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a common malignancy that is associated with poor prognosis in humans. Despite the development of targeted drugs, overall survival remains a significant challenge, and new therapeutic strategies are urgently needed. The aim of this study was to investigate the function of miR-552-5p in ferroptosis and the underlying mechanism, as well as to explore novel strategies for HCC treatment. CCK8 assay results showed that the viability of Huh-7 and Hep3B cells decreased significantly after transfection of the miR-552-5p inhibitor. In addition, we found that glutathione levels were depleted, intracellular Fe<sup>2+</sup> levels were elevated, and the mean fluorescence intensity of C11-BODIPY was increased after miR-552-5p transfection. Transmission electron microscopy revealed that mitochondria became smaller and mitochondrial membrane intensity was increased in the inhibitor+RSL3 group. Mechanistically, a dual-luciferase reporter assay confirmed that miR-552-5p interacted with the 3' untranslated region (3' UTR) of acyl-CoA synthetase long-chain family member 4 (<i>ACSL4</i>) mRNA. qPCR and Western blotting results verified that miR-552-5p negatively regulated ACSL4 expression. In addition, we found that overexpression of ZNF8, which is a transcription factor, reduced intracellular miR-552-5p levels and enhanced sensitivity to ferroptosis. miR-552-5p reduces sensitivity to ferroptosis by targeting the 3' UTR of <i>ACSL4</i> in HCC. The ZNF8-miR-552-5p-ACSL4 axis is involved in regulation of ferroptosis in HCC, and these findings may provide a new therapeutic target for treatment of HCC.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"336-347"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samir Andrade Mendonça, Fernanda Antunes, Otto L D Cerqueira, Paulo Roberto Del Valle, Aline Hunger, Percíllia V S de Oliveira, Barbara Brito, Eugenia Costanzi-Strauss, Bryan E Strauss
{"title":"Induction of Immune-Stimulating Factors and Oncolysis Upon p14<sup>ARF</sup> Gene Transfer in Melanoma Cell Lines.","authors":"Samir Andrade Mendonça, Fernanda Antunes, Otto L D Cerqueira, Paulo Roberto Del Valle, Aline Hunger, Percíllia V S de Oliveira, Barbara Brito, Eugenia Costanzi-Strauss, Bryan E Strauss","doi":"10.1089/dna.2022.0115","DOIUrl":"https://doi.org/10.1089/dna.2022.0115","url":null,"abstract":"<p><p>Together with an anti-tumor immune response, oncolysis using a recombinant viral vector promises to eliminate cancer cells by both gene transfer and host-mediated functions. In this study we explore oncolysis induced by nonreplicating adenoviral vectors used for p14<sup>ARF</sup> and interferon-β (hIFNβ) gene transfer in human melanoma cell lines, revealing an unexpected role for p14<sup>ARF</sup> in promoting cellular responses predictive of immune stimulation. Oncolysis was confirmed when UACC-62 (p53 wild-type) cells succumbed upon p14<sup>ARF</sup> gene transfer <i>in vitro</i>, whereas SK-Mel-29 (p53-mutant) benefitted from its combination with hIFNβ. In the case of UACC-62, <i>in situ</i> gene therapy in nude mice yielded reduced tumor progression in response to the p14<sup>ARF</sup> and hIFNβ combination. Potential for immune stimulation was revealed where p14<sup>ARF</sup> gene transfer <i>in vitro</i> was sufficient to induce emission of immunogenic cell death factors in UACC-62 and upregulate pro-immune genes, including IRF1, IRF7, IRF9, ISG15, TAP-1, and B2M. In SK-Mel-29, p14<sup>ARF</sup> gene transfer induced a subset of these factors. hIFNβ was, as expected, sufficient to induce these immune-stimulating genes in both cell lines. This work is a significant advancement for our melanoma gene therapy strategy because we revealed not only the induction of oncolysis, but also the potential contribution of p14<sup>ARF</sup> to immune stimulation.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"274-288"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endoplasmic Reticulum Stress: A Key Regulator of Cardiovascular Disease.","authors":"Zhao Chen, Shi-Liang Zhang","doi":"10.1089/dna.2022.0532","DOIUrl":"https://doi.org/10.1089/dna.2022.0532","url":null,"abstract":"<p><p>The problems associated with economic development and social progress have led to an increase in the occurrence of cardiovascular diseases (CVDs), which affect the health of an increasing number of people and are a leading cause of disease and population mortality worldwide. Endoplasmic reticulum stress (ERS), a hot topic of interest for scholars in recent years, has been confirmed in numerous studies to be an important pathogenetic basis for many metabolic diseases and play an important role in maintaining physiological processes. The endoplasmic reticulum (ER) is a major organelle that is involved in protein folding and modification synthesis, and ERS occurs when several physiological and pathological factors allow excessive amounts of unfolded/misfolded proteins to accumulate. ERS often leads to initiation of the unfolded protein response (UPR) in a bid to re-establish tissue homeostasis; however, UPR has been documented to induce vascular remodeling and cardiomyocyte damage under various pathological conditions, leading to or accelerating the development of CVDs such as hypertension, atherosclerosis, and heart failure. In this review, we summarize the latest knowledge gained concerning ERS in terms of cardiovascular system pathophysiology, and discuss the feasibility of targeting ERS as a novel therapeutic target for the treatment of CVDs. Investigation of ERS has immense potential as a new direction for future research involving lifestyle intervention, the use of existing drugs, and the development of novel drugs that target and inhibit ERS.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 6","pages":"322-335"},"PeriodicalIF":3.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9575484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Xu, Chutong Wang, Minying Li, Meili Yuan, Jing Wei, Baiqing Li, Zhongqing Qian, Ting Wang, Xiaojing Wang, Hongtao Wang
{"title":"<i>Mycobacterium tuberculosis</i> PE8 (Rv1040c) Promotes the Intracellular Survival of Recombinant Mycobacterium by Regulating Host Inflammatory Cytokines and Inhibiting Cell Late Apoptosis.","authors":"Tao Xu, Chutong Wang, Minying Li, Meili Yuan, Jing Wei, Baiqing Li, Zhongqing Qian, Ting Wang, Xiaojing Wang, Hongtao Wang","doi":"10.1089/dna.2022.0316","DOIUrl":"https://doi.org/10.1089/dna.2022.0316","url":null,"abstract":"<p><p>Tuberculosis is an important chronic and often fatal infectious disease mainly caused by the bacterium <i>Mycobacterium tuberculosis</i> (Mtb). Mtb is one of the most successful pathogens that harbors several potential virulence factors not found in nonpathogenic mycobacteria. As the Mtb cell envelope is closely associated with its virulence and resistance, it is very important to understand the cell envelope for better treatment of causative pathogen. There is increasing evidence that Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins are the major effectors of virulence and persistence encoded in the Mtb H37Rv genome. However, the function of PE8 has not been explored to date. In this study, we heterologously expressed PE8 in nonpathogenic, fast-growing <i>M. smegmatis</i> to investigate the interaction between PE8 and the host to determine its possible biological functions. We found that recombinant <i>M. smegmatis</i> cells expressing PE8 were less susceptible to sodium dodecyl sulfate-induced surface stress compared with those expressing the empty vector, suggesting that PE8 may be involved in stress responses. In addition, macrophages infected with PE8-expressing <i>M. smegmatis</i> produced obviously lower levels of the proinflammatory factor IL-1β, IL-6, and TNF-α and higher levels of the inhibitory factor IL-10. We further found that PE8 promoted <i>M. smegmatis</i> survival within macrophages by inhibiting late apoptosis of macrophages. Collectively, selective targeting of the PE/PPE protein family offers an untapped opportunity to the development of more effective and safer drugs against Mtb infection.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 5","pages":"254-264"},"PeriodicalIF":3.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Young Seok Eom, Byung Su Ko, Fahad Hassan Shah, Song Ja Kim
{"title":"E3 Ubiquitin Ligase Constitutive Photomorphogenic 1 Regulates Differentiation and Inflammation via MAPK Signaling Pathway in Rabbit Articular Chondrocytes.","authors":"Young Seok Eom, Byung Su Ko, Fahad Hassan Shah, Song Ja Kim","doi":"10.1089/dna.2022.0664","DOIUrl":"https://doi.org/10.1089/dna.2022.0664","url":null,"abstract":"Constitutive photomorphogenic 1 (COP1), is an E3 ubiquitin ligase that plays a role in the regulation of various cellular processes including cell growth, differentiation, and survival in mammals. In certain conditions such as overexpression or loss of function, COP1 acts either as an oncogenic protein or as a tumor suppressor by targeting specific proteins for ubiquitination-mediated degradation. However, the precise role of COP1 has not been well studied in primary articular chondrocytes. In this study, we investigated the role of COP1 in chondrocyte differentiation. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that COP1 overexpression reduced type II collagen expression, promoted cyclooxygenase 2 (COX-2) expression, and reduced sulfated proteoglycan synthesis, as detected by Alcian blue staining. Upon siRNA treatment, revived type II collagen, sulfated proteoglycan production, and decreased COX-2 expression. Phosphorylation of p38 kinase and ERK-1/-2 signaling pathways was regulated by COP1 upon cDNA and siRNA transfection in chondrocytes. The inhibition of the p38 kinase and ERK-1/-2 signaling pathways with SB203580 and PD98059 ameliorated the expression of type II collagen and COX-2 in transfected chondrocytes, thus suggesting that COP1 regulates differentiation and inflammation in rabbit articular chondrocytes via the p38 kinase and ERK-1/-2 signaling pathway.","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 5","pages":"239-247"},"PeriodicalIF":3.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9435945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}