Molecular Biology最新文献

{"title":"Cytoplasmic mRNA Transport: Adaptors of mRNA Binding to Microtubule Motor Proteins","authors":"Y. A. Vdovina, S. G. Georgieva, D. V. Kopytova","doi":"10.1134/s0026893324700018","DOIUrl":"https://doi.org/10.1134/s0026893324700018","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The process of mRNA localization in the cytoplasm involves the directed transport of mRNP particles using the microtubule system. This transport is mediated and regulated by specific factors—adaptors between mRNA molecules and microtubule motor proteins. Adaptors are a key link in the mechanism of mRNA transport, but to date their identity and functioning are mostly unknown. In this review, we examine the features and importance of adaptor proteins in mRNA transport during oogenesis and in neuronal function. This article summarizes recent data on mRNA binding adaptors in the cytoplasm and the mechanisms of their interaction with microtubule motor proteins.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"48 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254093","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":"DNA Methylation Profiling in Aneurysm and Comorbid Atherosclerosis of the Ascending Aorta","authors":"I. A. Goncharova, A. A. Zarubin, S. A. Shipulina, Iu. A. Koroleva, D. S. Panfilov, B. N. Kozlov, M. S. Nazarenko","doi":"10.1134/s0026893324700079","DOIUrl":"https://doi.org/10.1134/s0026893324700079","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Atherosclerosis and aneurysm of the aorta are relatively common pathological conditions that remain asymptomatic for a long period of time and have life-threatening and disabling complications. DNA methylation profiling in several regions (a dilated area, a nondilated area, and an atherosclerotic plaque) of the ascending aorta was carried out in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). Differences in methylation level between dilated and normal aortic tissues were detected for two CpG sites of the <i>NR2F1-AS1</i> gene (|Δβ| ≥ 0.2 and <i>FDR</i> &lt; 0.05). In total, 586/480 differentially methylated CpG sites (DMSs) were identified by comparing atherosclerotic plaque samples with dilated/normal aortic tissues; 323/234 of the DMSs were hypermethylated and 263/246 were hypomethylated in atherosclerotic plaques. Most DMSs were in introns and intergenic regions; 88.2% of the DMSs were in the binding sites of transcription factors, among which ZNf263, ZFP148, PATZ1, NRF1, TCF12, and EGR1 play a role in the pathogenesis of atherosclerosis of various arteries and ELK1, ETS1, and KLF15 play a role in aortic aneurysms. Sixteen DMSs were found in the regions of the genes <i>CMIP</i>, <i>RPH3AL</i>, <i>XRCC1</i>, <i>GATA5</i>, <i>EXD3</i>, <i>KCNC2</i>, <i>HIVEP3</i>, <i>ADCY9</i>, <i>CDCP2</i>, <i>FOLR1</i>, <i>WT1</i>, <i>MGMT</i>, <i>GAS2</i>, <i>CA1</i>, <i>PRSS16</i>, and <i>ANK3</i>, whose protein products are involved in both aortic dissection and atherosclerosis in various arterial circulation regions. The protein products of the genes are involved in a wide range of biological processes, including mesenchyme development (GO:0060485; <i>FOLR1</i>, <i>WT1</i>, <i>GATA5</i>, <i>HIVEP3</i>, and <i>KCNC2</i>) and positive regulation of DNA metabolic processes (GO:0051054; <i>MGMT</i>, <i>WT1</i>, and <i>XRCC1</i>).</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"35 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254088","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":"Methylation of Long Noncoding RNA Genes SNHG6, SNHG12, and TINCR in Ovarian Cancer","authors":"S. S. Lukina, A. M. Burdennyy, E. A. Filippova, L. A. Uroshlev, I. V. Pronina, N. A. Ivanova, M. V. Fridman, K. I. Zhordania, T. P. Kazubskaya, N. E. Kushlinskii, V. I. Loginov, E. A. Braga","doi":"10.1134/s0026893324700067","DOIUrl":"https://doi.org/10.1134/s0026893324700067","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Ovarian cancer (OC) develops asymptomatically and escapes diagnosis until advanced stages, the feature contributing to a higher mortality rate. New prospects of OC diagnosis and treatment have been opened in studies of the gene regulation mechanisms that involve long noncoding RNAs (lncRNAs) and identification of the lncRNA genes that are inhibited via methylation of the promoter region. A set of 122 samples of primary OC tumors was examined by methylation specific real-time PCR to assess the methylation level of the lncRNA genes <i>PLUT</i>, <i>SNHG1</i>, <i>SNHG6</i>, <i>SNHG12,</i> and <i>TINCR</i>. A significant increase in their methylation levels was observed in OC (<i>p</i> &lt; 0.001 by the nonparametric Mann–Whitney test). The methylation levels of <i>SNHG6</i>, <i>SNHG12</i>, and <i>TINCR</i> were found to correlate significantly (<i>p</i> &lt; 0.05) with the stage of the tumor process, the histological grade, and metastasis. Downregulation of <i>SNHG6</i>, <i>SNHG12</i>, and <i>TINCR</i> was detected by real-time RT–qPCR, and a significant correlation between methylation and expression was demonstrated for <i>SNHG6</i> and <i>TINCR</i> (<i>r</i>_s ≤ –0.5, <i>p</i> &lt; 0.001). The respective lncRNA genes were assumed to provide potential epigenetic markers of OC.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"27 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259723","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":"SMURF1-Interference Effects Autophagy and Pulmonary Fibrosis through SMAD7 and the TGF-β1/SMAD Pathway","authors":"L. Lin, D. Xue, L.-M. Chen, Q.-Y. Wei, J.-H. Chen, Y. Li, X.-L. Ye, Z.-H. Huang","doi":"10.1134/s002689332470033x","DOIUrl":"https://doi.org/10.1134/s002689332470033x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>SMAD-specific E3 ubiquitin proten ligase 1 (SMURF1) is involved in transforming growth factor (TGF)-β1/Smad pathway-mediated tissue fibrosis. However, its role in pulmonary fibrosis and the related molecular mechanisms are still unclear. This study aims to investigate whether SMURF1 inhibits autophagy and promotes pulmonary fibrosis via SMAD family member 7 (SMAD7) and TGF-β1/SMAD signal pathway. MRC-5 cells were treated with TGF-β1 followed by <i>MURF1-</i>interference. The rate of cell migration was assessed using the cell scratch test. Autophagosomes were analyzed using a transmission electron microscope. mRNA levels of SMURF1, SMAD7, TGF-β1, phosphorylated (p)-SMAD1, p-SMAD3, α-smooth muscle actin (α-SMA), matrix metallopeptidase 7 (MMP7), microtubule-associated protein light chain 3 (LC3 ) and Beclin1 were evaluated by quantitative real-time PCR (qPCR), Western blotting, and immunofluorescence. The interaction between SMURF1 and SMAD7 was investigated in a co-immunoprecipitation (Co-IP) experiment. We found that after TGF-β1 treatment, the mRNA levels of SMURF1, α-SMA, MMP7, and p-Smad1/3 were increased, and the levels of Beclin1 and LC3 were decreased. Apart from these, cell autophagy was decreased, while the migration ability was increased. After SMURF1-interference, SMURF1, α-SMA and MMP7 mRNA levels were significantly decreased, p-SMAD1 was slightly reduced, and p-Smad3 was not changed. As for Beclin1 and LC3, their transcription increased, cell autophagy increased, and migratory ability decreased. The interaction between SMURF1 and Smad7 was confirmed by Co-IP. In conclusion, SMURF1 may inhibit autophagy and promote lung fibrosis by downregulating <i>SMAD7</i> and activating the TGF-β1/SMAD pathway. These results may serve as a basis for the development of new therapeutic targets in the pulmonary fibrosis clinic.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"75 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885193","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":"Exploring the Potential Mechanism of Apoptosis Induced by MFSD8 in Endothelial Cells: an RNA Sequencing and Bioinformatics Analysis","authors":"Q. Xiang, Y. Liu, S. S. Jiang, Y. F. Chen, Y. X. Liu, D. W. Yang, L. Tang, J. M. Li","doi":"10.1134/s0026893324700225","DOIUrl":"https://doi.org/10.1134/s0026893324700225","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Neuronal ceroid lipofuscinoses (NCLs) belong to a group of inherited neurodegenerative disorders without effective treatments. Though loss-of-function in the <i>MFSD8</i> gene resulting in a variant late-infantile subtype of NCLs is well documented, its roles remain poorly explored and understood. The results showed an increased cell apoptosis rate after the <i>MFSD8</i> gene low expression in HUVECs by Flow cytometric analysis. RNA sequencing revealed 367 differentially expressed genes upon the <i>MFSD8</i> gene overexpression in HUVECs. Bioinformatics analyses revealed that the <i>MFSD8</i> gene overexpression might be involved in the PI3K/Akt signaling pathway, and interleukin-6 (<i>IL-6</i>), interleukin-1 beta (<i>IL-1B</i>), fibronectin 1 (<i>FN1</i>), fibroblast growth factor 2 (<i>FGF2</i>), toll-like receptor 4 (<i>TLR4</i>), tumor necrosis factor (<i>TNF</i>), and prostaglandin G/H synthase 2 (<i>PTGS2</i>) were the potential hub genes affected by the <i>MFSD8</i> gene. Gene set enrichment analysis and qRT-PCR assay validation also disclosed that the “Hallmark_Apoptosis” pathway was dramatically enriched in differentially expressed genes. The results revealed that the loss of functional MFSD8 protein indirectly or directly increased the apoptosis of HUVECs, indicating that the expression of the <i>MFSD8</i> gene was essential for cell survival. The hub genes, including <i>IL-6</i>, <i>IL-1B</i>, <i>FN1</i>, <i>FGF2</i>, <i>TLR4</i>, <i>TNF</i>, and <i>PTGS2</i>, might provide insight into the apoptosis induced by the <i>MFSD8</i> gene in NCLs. Although many experiments are required to validate these predictions, the results may help investigate the roles of the <i>MFSD8</i> gene on apoptosis and the corresponding mechanism.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"148 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885138","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":"Global Transcriptome Analysis Reveals Corresponding Genes and Key Pathways Involved in Oxidative Stress in Mouse Small Intestinal Cells","authors":"Y. He, C. P. Feng, J. L. Li, R. Du","doi":"10.1134/s0026893324700365","DOIUrl":"https://doi.org/10.1134/s0026893324700365","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Understanding the molecular mechanisms involved in the effects of oxidative stress in humans and animals is important to minimize the damage it causes, leading to various intestinal diseases. Our aim is to study the genes and pathways involved in oxidative stress in the gut using mouse small intestinal epithelial cells (MODE-K) as a model. The MODE-K cell line was divided into two different groups: one group was treated with hydrogen peroxide (H₂O₂) and the other group was not. To analyze the effects of H₂O₂ exposure, cell viability, apoptosis rate and reactive oxygen species (ROS) levels were determined. Next, transcriptome sequencing was performed, differentially expressed genes (DEGs) were identified and function annotation was performed, followed by a series of bioinformatics analyses. Real-time PCR was used to confirm the transcriptome data. Our results showed that H₂O₂-induced oxidative stress significantly increased ROS synthesis and promoted cell apoptosis in mouse small intestinal epithelial cells. During oxidative stress, 1207 DEGs (859 up-regulated, 348 down-regulated) were identified. According to GO analysis, DEGs are annotated into 51 different GO classifications including 22 biological processes, 15 cellular components and 14 molecular functions. In addition, using KEGG, PPI and correlation analysis, the two most significant subnetworks were identified. Ten correlated nodal DEGs of the first subnetwork correspond to MAPK, NF-kappa B and PI3K-AKT signaling pathways, and six correlated DEGs of the second subnetwork are associated with mitochondria. KDM6B was found to link these two subnetworks. The results suggest that oxidative stress affects epithelial growth, metabolism and apoptosis in a mouse model of intestinal cells through signaling pathways such as MAPK and PI3K/AKT/NF-kappa B, and mitochondria-related genes that are interconnected through the PTGS2-KDM6B-MT-ATP6 pathway.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"22 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885487","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":"Microtubule-Associated Protein 9 Is a Potential Tumor Suppressor That Is Inactivated by Methylation in Cervical Cancer","authors":"P. Li, F. Wang, Y. Y. Gao, W. Zhang, Y. Zhang","doi":"10.1134/s0026893324700304","DOIUrl":"https://doi.org/10.1134/s0026893324700304","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Cervical cancer is a malignant disease that seriously affects women’s health, and the cause of cervical cancer is complex. Microtubule-associated protein 9 (MAP9) localizes to the mitotic spindle and it plays an important role in spindle assembly and centrosome integrity maintenance. The expression and function of MAP9 is unclear in cervical cancer. This study aims to explore the relationship between DNA methylation of <i>MAP9</i> and cervical cancer, and the function of MAP9 in cervical cancer. qRT-PCR was used to detect the transcriptional expression of <i>MAP9</i> in cervical cancer tissues and cell lines. The methylation status of <i>MAP9</i> promoter was determined by bisulfite sequencing PCR (BSP). The DNA methyltransferase inhibitor, 5-Aza-CdR, was used to inhibit the activity of methyltransferase. Then, the cell proliferation was performed by CCK-8 assay after the transfection of <i>MAP9</i> plasmids. Furthermore, the cell cycle and apoptosis were performed by flow cytometry. It was found that <i>MAP9</i> was down-regulated both in cervical cancer tissues and cell lines. The promoter and the first exon region of <i>MAP9</i> was hypermethylated and its mRNA expression could be restored after the treatment of 5-Aza-CdR. Ectopic expression of <i>MAP9</i> could inhibit cell proliferation and cell cycle, without effecting the cell apoptosis. The low expression of <i>MAP9</i> in cervical cancer dues to its hypermethylation and acts a potential tumor suppressor gene. MAP9 might be a novel biomarker in cervical cancer.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"38 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885136","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":"P3H4 Regulates Apoptosis and Autophagy of Breast Cancer Cells via BCL-2/BAX/Caspase-3 and AMPK/mTOR/ULK1 Signaling Pathways","authors":"T. Wang, M. M. Li, Z. Dong, D. M. Zhu","doi":"10.1134/s0026893324700237","DOIUrl":"https://doi.org/10.1134/s0026893324700237","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The role of prolyl 3-hydroxylase family member 4 (P3H4, or SC65) in breast cancer and the molecular mechanisms in which this protein was involved were investigated. For this purpose, microchips with cancerous and paracancerous tissues collected from 56 patients with breast cancer were constructed. The P3H4 protein expression was evaluated by immunohistochemistry. Cell lines with decreased and increased P3H4 expression were selected and divided into five groups: <i>P3H4</i> overexpression and corresponding negative control, <i>P3H4</i> knockout groups #1 and #2 and corresponding negative control. CCK8 assay, colony formation test, immunoblotting, scratch test, transwell test and flow cytometry were used to determine the relevant cell functions. P3H4 expression was higher in breast cancer cells than in paracancerous tissue. Compared with corresponding negative control, proliferative activity of the cells was inhibited at 24, 48 and 72 h, migration activity and invasion ability of the cells were reduced, autophagy and apoptosis in the cells were increased in <i>P3H4</i> knockout groups #1 and #2. <i>P3H4</i> knockout promoted apoptosis of breast cancer cells and inhibited their proliferation, migration, and invasion by activating the BCL-2/BAX/Caspase-3 and AMPK/mTOR pathways. <i>P3H4</i> knockout promoted apparently autophagy by activating the AMPK/mTOR/ULK1 pathway. However, <i>P3H4</i> overexpression could promote the proliferation, migration and invasion of breast cancer cells, and inhibited apoptosis and autophagy of mammary gland adenocarcinoma cells MDA-MB-231.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"109 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885191","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":"Ginkgo biloba Leaf Polysaccharide Induces Autophagy and Modulates the Expression of Apoptosis Markers in Hepatocellular Carcinoma Cells","authors":"K. Li, Z. F. Yu, K. X. Zhang, Z. H. Li, X. C. Liu, B. Y. Li, Y. X. Feng, K. F. Wei, Z. G. Yan","doi":"10.1134/s0026893324700328","DOIUrl":"https://doi.org/10.1134/s0026893324700328","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and poses a severe threat to human health. <i>Ginkgo biloba</i> leaf polysaccharide (GBLP) is a bioactive component, and its sulphated derivative (sulfated GBLP, SGBLP) may exhibit high antitumor activity in certain types of cancers. However, the precise mechanisms of the SGBLP antitumor activity, particularly in HCC, remain unclear. Here, we assessed the effect of SGBLP on HepG2 hepatocellular carcinoma cells. SGBLP was shown to inhibit cellular proliferation and promote apoptosis through the regulation of pro- as well as anti-apoptosis markers, and to induce autophagy by supressing the PI3K/AKT/mTOR pathway. In addition, the autophagy inhibitor 3-melyladenine (3-MA) enhanced the antiproliferative and proapoptotic effects of SGBLP in HepG2 cells. Thus, SGBLP exhibits antitumor activity, and its combination with an autophagy inhibitor may represent a promising anticancer strategy in the treatment of HCC.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"53 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885488","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":"Cytotoxicity Studies of 5-Arylaminouracil Derivatives","authors":"V. A. Kezin, E. S. Matyugina, S. A. Surzhikov, M. S. Novikov, A. A. Maslova, I. L. Karpenko, A. V. Ivanov, S. N. Kochetkov, A. L. Khandazhinskaya","doi":"10.1134/s0026893324020079","DOIUrl":"https://doi.org/10.1134/s0026893324020079","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138). Cytotoxicity assessment by the standard MTT test showed that most of the compounds lack significant toxicity towards the above cells. However, 5-(4-isopropylphenylamine)uracil and 5‑(4-tert-butylphenylamine)uracil exhibited a dose-dependent toxic effect towards the GBM6138 cell line with half-maximal inhibitory concentrations (IC₅₀) of 9 and 2.3 μM, respectively. Antitumor activity was for the first time demonstrated for compounds of this type and can serve as a starting point for further research.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"14 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592223","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}