{"title":"The Tumor Suppressor Roles and Mechanisms of MiR-491 in Human Cancers.","authors":"Farzad Sadri, Seyede Fatemeh Hosseini, Atena Aghayei, Mohammad Fereidouni, Zohreh Rezaei","doi":"10.1089/dna.2022.0274","DOIUrl":"https://doi.org/10.1089/dna.2022.0274","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are short non-coding RNAs that bind to the 3' untranslated region (3'' UTR) of target mRNAs to control gene expression post-transcriptionally. Recent indications have highlighted their important roles in a variety of pathophysiological conditions as well as human malignancies. Dysregulated miRNAs act as tumor suppressor genes or oncogenes in a variety of cancers. MiR-491 has been shown to have a major effect on tumorigenesis in multiple malignancies through binding to specific genes and signaling cascades, thereby preventing cancer progression. This review provides an overview of miR-491 expression in regulatory mechanisms and biological procedures of tumor cells, as well as the prospective possible treatment effects of various types of human cancers.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 9","pages":"810-823"},"PeriodicalIF":3.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40684082","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":"4'-Fluorouridine Is a Broad-Spectrum Orally Available First-Line Antiviral That May Improve Pandemic Preparedness.","authors":"Carolin M Lieber, Richard K Plemper","doi":"10.1089/dna.2022.0312","DOIUrl":"https://doi.org/10.1089/dna.2022.0312","url":null,"abstract":"<p><p>The COVID-19 pandemic has highlighted the urgent need for the development of broad-spectrum antivirals to enhance preparedness against future spillover of zoonotic viruses with pandemic potential into the human population. Currently, the direct-acting orally available SARS-CoV-2 inhibitors molnupiravir and paxlovid are approved for human use under emergency use authorization. A promising next-generation therapeutic candidate is the orally available ribonucleoside analog 4'-fluorouridine (4'-FlU) that had potent antiviral efficacy against different viral targets, including SARS-CoV-2 in human organoids and animal models. Although a nucleoside analog inhibitor such as molnupiravir that targets the viral RNA-dependent RNA polymerase (RdRP) complex, 4'-FlU showed a distinct mechanism of activity, delayed chain termination, compared with molnupiravir's induction of viral error catastrophe. This review will focus on some currently approved and emerging medicines developed against SARS-CoV-2, examining their potential to form a pharmacological first-line defense against zoonotic viruses with pandemic potential.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 8","pages":"699-704"},"PeriodicalIF":3.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416544/pdf/dna.2022.0312.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Doudou Huang, Chi Zhang, Panpan Wang, Xiting Li, Li Gao, Chuanjiang Zhao
{"title":"JMJD3 Promotes <i>Porphyromonas gingivalis</i> Lipopolysaccharide-Induced Th17-Cell Differentiation by Modulating the STAT3-RORc Signaling Pathway.","authors":"Doudou Huang, Chi Zhang, Panpan Wang, Xiting Li, Li Gao, Chuanjiang Zhao","doi":"10.1089/dna.2022.0149","DOIUrl":"https://doi.org/10.1089/dna.2022.0149","url":null,"abstract":"<p><p>The immune response mediated by Th17 cells is essential in the pathogenesis of periodontitis. Emerging evidence has demonstrated that lipopolysaccharide from <i>Porphyromonas gingivalis</i> (Pg-LPS) could promote Th17-cell differentiation directly, while the downstream signaling remains elusive. This study was aimed to explore the role of JMJD3 (a JmjC family histone demethylase) and signal transducers and activators of transcription 3 (STAT3) in Th17-cell differentiation triggered by Pg-LPS and clarify the interaction between them. We found that the expression of JMJD3 and STAT3 was significantly increased under Th17-polarizing conditions. Pg-LPS could promote Th17-cell differentiation from CD4<sup>+</sup> T cells, with an increased expression of JMJD3 and STAT3 compared to the culture without Pg-LPS. The coimmunoprecipitation results showed that the interactions of JMJD3 and STAT3, STAT3 and retinoid-related orphan nuclear receptor γt (RORγt) were enhanced following Pg-LPS stimulation during Th17-cell differentiation. Further blocking assays were performed and the results showed that inhibition of STAT3 or JMJD3 both suppressed the Th17-cell differentiation, JMJD3 inhibitor could reduce the expression of STAT3 and p-STAT3, while JMJD3 expression was not affected when STAT3 was inhibited. Taken together, this study found that JMJD3 could promote Pg-LPS induced Th17-cell differentiation by modulating the STAT3-RORc signaling pathway.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 8","pages":"778-787"},"PeriodicalIF":3.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416562/pdf/dna.2022.0149.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10272110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FOXM1 Promotes Malignant Proliferation of Esophageal Squamous Cell Carcinoma Through Transcriptional Activating CDC6.","authors":"Xiongfeng Chen, Jingbo Chen, Xunbin Yu, Guishan Lin, Ting Chen","doi":"10.1089/dna.2022.0169","DOIUrl":"https://doi.org/10.1089/dna.2022.0169","url":null,"abstract":"<p><p>Forkhead box M1 (FOXM1) is a proliferative transcription factor and plays a vital role in many cancers. However, the function and molecular mechanism of FOXM1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Hence, we aim to clarify the molecular basis of FOXM1-mediated ESCC progression. In this study, bioinformatics analysis showed that FOXM1 was mainly involved in key signal pathways, including cell proliferation, cell cycle, and homologous recombination in ESCC, and predicted that CDC6 might be a potential regulatory target gene of FOXM1. The results revealed that FOXM1 and CDC6 were significantly overexpressed in ESCC tissue and cell line, and their expression was positively correlated. Further studies showed that FOXM1 directly transcriptionally activated CDC6 by binding to its promoter region in ESCC cells. Moreover, FOXM1 mediated ESCC cell proliferation by regulating CDC6 expression, which may be related to promoting G1-S phase transition of cell cycle. Taken together, FOXM1-CDC6 axis mediates ESCC malignant proliferation and may serve as a potential biological target for ESCC treatment.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 7","pages":"671-682"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293688/pdf/dna.2022.0169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10107702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zijun Xiao, Shanshan Wei, Jie Huang, Jiaqin Liu, Jian Liu, Bikui Zhang, Wenqun Li
{"title":"Noncoding RNA-Associated Competing Endogenous RNA Networks in Doxorubicin-Induced Cardiotoxicity.","authors":"Zijun Xiao, Shanshan Wei, Jie Huang, Jiaqin Liu, Jian Liu, Bikui Zhang, Wenqun Li","doi":"10.1089/dna.2022.0022","DOIUrl":"https://doi.org/10.1089/dna.2022.0022","url":null,"abstract":"<p><p>Accumulating evidence has indicated that noncoding RNAs (ncRNAs) are involved in doxorubicin-induced cardiotoxicity (DIC). However, the ncRNA-associated competing endogenous RNA (ceRNA)-mediated regulatory mechanisms in DIC remain unclear. In this study, we aimed to systematically investigate the alterations in expression levels of long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and mRNA in a DIC mouse model through deep RNA sequencing (RNA-seq). The results showed that 217 lncRNAs, 41 circRNAs, 11 miRNAs and 3633 mRNAs were aberrantly expressed. Moreover, the expression of 12 randomly selected transcripts was determined by real-time quantitative polymerase chain reaction to test the reliability of RNA-seq data. Based on the interaction between miRNAs and mRNAs, as well as lncRNAs/circRNAs and miRNAs, we constructed comprehensive lncRNA or circRNA-associated ceRNA networks in DIC mice. Moreover, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for differentially expressed genes. In conclusion, these identified ceRNA interactions provide new insight into the underlying mechanism and may be crucial therapeutic targets of DIC.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 7","pages":"657-670"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9262105","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":"Dihydroartemisinin Triggers Ferroptosis in Multidrug-Resistant Leukemia Cells.","authors":"Xueyan Zhang, Ziying Ai, Zhewen Zhang, Rui Dong, Lina Wang, Suya Jin, Hulai Wei","doi":"10.1089/dna.2021.1145","DOIUrl":"https://doi.org/10.1089/dna.2021.1145","url":null,"abstract":"The molecular mechanisms and role of ferroptosis in tumor drug resistance remain unclear. In this study, we found that multidrug-resistant (MDR) K562/adriamycin (ADM) leukemia cells possessed higher glutathione (GSH) levels and iron-regulatory protein 2 (IRP2), transferrin receptor, ferritin heavy chain 1 (FTH1), and peroxidase-4 (GPX4) expression than parental drug-sensitive K562 leukemia cells. These elevations might have increased the antioxidant ability of K562/ADM cells and granted them increased buffering capacity against iron disorder, protecting them from ferroptosis and favoring drug resistance. However, dihydroartemisinin (DHA) restrained MDR K562/ADM cell viability and enhanced the sensitivity to ADM by strengthening ferroptosis induced by downregulation of GSH levels and GPX4, IRP2, and FTH expression, upregulation of reactive oxygen species (ROS) levels, and the consequent suppression of total serine/threonine kinase (AKT), total mammalian target of rapamycin (t-mTOR), phosphorylated mTOR (p-mTOR), and p-mTOR/t-mTOR levels. Moreover, compared with K562 cells, MDR K562/ADM cells exhibited greater ROS increases, GSH decreases, and viability rescue after ferroptosis inhibitor treatment owing to further suppression of FTH1, GPX4, p-mTOR, and p-mTOR/t-mTOR. Collectively, the increase in oxidative damage and the blockade of antioxidant defence shaped DHA-induced ferroptosis, which was responsible for the sensitivity of MDR leukemia cells to DHA. Regulating iron homeostasis/ROS/AKT/mTOR might be a potential chemotherapeutic strategy for sensitizing drug-resistant leukemia.","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48071368","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}
Jun Yang, Wuju Zhang, Eryong Lai, Wen Liu, Pinglin Lai, Zhipeng Zou, Weidong Wang, X. Bai
{"title":"Deletion of Rheb1 in Osteocytes Leads to Osteopenia Characterized by Reduced Bone Formation and Enhanced Bone Resorption.","authors":"Jun Yang, Wuju Zhang, Eryong Lai, Wen Liu, Pinglin Lai, Zhipeng Zou, Weidong Wang, X. Bai","doi":"10.1089/dna.2021.0874","DOIUrl":"https://doi.org/10.1089/dna.2021.0874","url":null,"abstract":"Ras homologue enriched in brain 1 (Rheb1), an upstream activator of the mechanistic target of rapamycin complex 1 (mTORC1), is known to modulate various cellular processes. However, its impact on bone metabolism in vivo remains unknown. The study aimed at understanding the role of Rheb1 on bone homeostasis. We measured the serum parameters and performed histomorphometry, quantitative real-time polymerase chain reaction, and Western blotting, along with the generation of mouse gene knockout (KO) model, and conducted a microcomputed tomography analysis and tartrate-resistant acid phosphatase staining, to delineate the impacts of Rheb1 on bone homeostasis. In the Rheb1 KO mice, the results showed that Rheb1 KO caused significant damage to the bone microarchitecture, indicating that mTORC1 activity was essential for the regulation of bone homeostasis. Specifically, suppressed mineralization activity in primary osteoblasts and a decreased osteoblast number were observed in the Rheb1 KO mice, demonstrating that loss of Rheb1 led to impaired osteoblastic differentiation. Furthermore, the higher apoptotic ratio in Rheb1-null osteocytes could promote Tnfsf11 expression and lead to an increase in osteoclasts, indicating increased bone resorption activity in the KO mice. The findings confirmed that Rheb1 deletion in osteoblasts/osteocytes led to osteopenia due to impaired bone formation and enhanced bone resorption.","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49584036","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":"Characterization and Functional Analysis of <i>ZmSWEET15a</i> in Maize.","authors":"Mengtong Liu, Tongyu Liu, Jianyu Lu, Yangyang Zhou, Shubo Liu, Peng Jiao, Siyan Liu, Jing Qu, Shuyan Guan, Yiyong Ma","doi":"10.1089/dna.2021.1144","DOIUrl":"https://doi.org/10.1089/dna.2021.1144","url":null,"abstract":"<p><p>The sugars will eventually be exported transporters (SWEETs) gene family is a new type of sugar transporters, which plays an important role in plant growth and development, physiological metabolism, and abiotic stress. In this study, we used quantitative real-time PCR to analyze the expression of <i>ZmSWEET15a</i> gene in different organs of maize and under different abiotic stresses. The results showed that <i>ZmSWEET15a</i> was expressed in roots, stems, leaves, and grains, with the highest expression level in leaves, which was highly correlated with leaf development. Under the treatment of polyethylene glycol (PEG), NaCl, H<sub>2</sub>O<sub>2</sub>, and abscisic acid stress, the expression of <i>ZmSWEET15a</i> was upregulated, while under the treatment of cold stress, the expression of <i>ZmSWEET15a</i> was inhibited. In sugar-specific experiments, we found that sucrose was the most effective carbon source for maize seed germination. The expression analysis of <i>ZmSWEET15a</i> in different carbon sources suggested that the expression of <i>ZmSWEET15a</i> was more likely to be induced by sucrose. Overexpression of <i>ZmSWEET15a</i> in maize plants could reduce the sucrose content in leaves and increase the sucrose content in grains. The heterologous expression of <i>ZmSWEET15a</i> in the yeast mutant strain SUSY7/ura indicated that <i>ZmSWEET15a</i> is a sucrose transporter and pH independent. This study provides new insight into sugar transport and carbohydrate partitioning in maize and other crops, and provide more genetic information for improving crop quality at the molecular level.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 6","pages":"564-574"},"PeriodicalIF":3.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245729/pdf/dna.2021.1144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9560349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omid Kooshkaki, A. Asghari, R. Mahdavi, Ghodsiyeh Azarkar, N. Parsamanesh
{"title":"Potential of MicroRNAs As Biomarkers and Therapeutic Targets in Respiratory Viruses: A Literature Review.","authors":"Omid Kooshkaki, A. Asghari, R. Mahdavi, Ghodsiyeh Azarkar, N. Parsamanesh","doi":"10.1089/dna.2021.1101","DOIUrl":"https://doi.org/10.1089/dna.2021.1101","url":null,"abstract":"MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through recognition of cognate sequences and interference of transcriptional, translational, or epigenetic processes. Hundreds of miRNA genes have been found in diverse viruses, and many of these are phylogenetically conserved. Respiratory viruses are the most frequent causative agents of disease in humans, with a significant impact on morbidity and mortality worldwide. Recently, the role of miRNAs in respiratory viral gene regulation, as well as host gene regulation during disease progression, has become a field of interest. This review highlighted the importance of various miRNAs and their potential role in fighting with respiratory viruses as therapeutic molecules with a focus on COVID-19.","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 6 1","pages":"544-563"},"PeriodicalIF":3.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46828360","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":"Identification of Genes with Altered Methylation in Osteoclast Differentiation and Its Roles in Osteoporosis.","authors":"Renpeng Peng, Yimin Dong, Honglei Kang, Qian Guo, Meipeng Zhu, Feng Li","doi":"10.1089/dna.2021.0699","DOIUrl":"https://doi.org/10.1089/dna.2021.0699","url":null,"abstract":"Osteoporosis is one of the most common metabolic skeletal diseases, which affects more than 200 million people worldwide, especially elderly and postmenopausal women. One of the main processes of osteoporosis is attenuated bone formation. Abundant evidence has confirmed that overactivated osteoclasts are responsible for the attenuated bone formation. This study aims at identifying novel methylation-associated biomarkers and therapeutic targets in osteoclasts by integrally analyzing methylation profiles and gene expression data. DNA methylation profile and gene expression data were obtained from the Gene Expression Omnibus (GEO) database. Subsequently, we integrated the two sets of data to screen for differentially expressed genes with differential methylation level (DM-DEGs) between osteoclasts and CD14+ monocytes from donors. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to uncover the enriched functions and pathways of identified DM-DEGs. In addition, by combining protein-protein interaction analysis and receiver-operator characteristic analysis, we finally identified four hub DM-DEGs. Gene Set Enrichment Analysis was utilized to validate and investigate the potential biological functions of the four hub DM-DEGs. Finally, Real-time quantitative PCR (QPCR) was performed to validate the mRNA expression level of the four identified hub DM-DEGs during osteoclast differentiation. CCRL2, CCL18, C1QB, and SELL were highly correlated with osteoclastic differentiation and osteoporosis phenotype. QPCR revealed that the expression of CCRL2, CCL18, and C1QB was increased during osteoclast differentiation, whereas the expression of SELL was decreased. The present study indicated a connection between gene expression and DNA methylation during osteoclast differentiation and that four hub DM-DEGs in osteoclastogenesis and osteoporosis pathogenesis might be potential candidates for intensive research and therapeutic targets for the treatment of osteoporosis.","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"41 6 1","pages":"575-589"},"PeriodicalIF":3.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45642459","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}