Journal of Biomedical Science最新文献

{"title":"Advances in nucleic acid-based cancer vaccines.","authors":"Hung-Chun Liao, Shih-Jen Liu","doi":"10.1186/s12929-024-01102-w","DOIUrl":"10.1186/s12929-024-01102-w","url":null,"abstract":"<p><p>Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"10"},"PeriodicalIF":9.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis.","authors":"Xuejie Gao, Qilin Feng, Qikai Zhang, Yifei Zhang, Chaolu Hu, Li Zhang, Hui Zhang, Guanli Wang, Ke Hu, Mengmeng Ma, Zhuning Wang, Yujie Liu, Dong An, Hongfei Yi, Yu Peng, Xiaosong Wu, Gege Chen, Xinyan Jia, Haiyan Cai, Jumei Shi","doi":"10.1186/s12929-024-01101-x","DOIUrl":"https://doi.org/10.1186/s12929-024-01101-x","url":null,"abstract":"<p><strong>Background: </strong>Enolase 1 (ENO1) is a conserved glycolytic enzyme that regulates glycolysis metabolism. However, its role beyond glycolysis in the pathophysiology of multiple myeloma (MM) remains largely elusive. Herein, this study aimed to elucidate the function of ENO1 in MM, particularly its impact on mitophagy under bortezomib-induced apoptosis.</p><p><strong>Methods: </strong>The bone marrow of clinical MM patients and healthy normal donors was used to compare the expression level of ENO1. Using online databases, we conducted an analysis to examine the correlation between ENO1 expression and both clinicopathological characteristics and patient outcomes. To investigate the biological functions of ENO1 in MM and the underlying molecular mechanisms involved, we conducted the following experiment: construction of a subcutaneous graft tumor model, co-immunoprecipitation, western blot, quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry, and cell functional assays.</p><p><strong>Results: </strong>ENO1 was identified as an unfavorable prognostic factor in MM. ENO1 knockdown suppresses tumorigenicity and causes cell cycle arrest. Inhibition of ENO1-regulated mitophagy sensitizes tumor cells to apoptosis. ENO1 enhanced the stability of the YWHAZ protein by increasing the acetylation of lysine in YWHAZ while antagonizing its ubiquitination, which in turn promoted mitophagy. HDAC6 mediates the deacetylation of YWHAZ by deacetylating the K138 site of YWHAZ. Inhibition of HDAC6 increased YWHAZ acetylation and decreased YWHAZ ubiquitination. Furthermore, combination treatment with bortezomib and pharmaceutical agents targeting ENO1 has synergistic anti-MM effects both in vivo and in vitro.</p><p><strong>Conclusion: </strong>Our data suggest that ENO1 promotes MM tumorigenesis and progression. ENO1 activates mitophagy by promoting the stability of YWHAZ and inhibits apoptosis and thus, leads to the drug resistance. ENO1-dependent mitophagy promotes MM proliferation and suppresses the level of bortezomib-induced apoptosis. Inhibition of ENO1 may represent a potential strategy to reverse the resistance of MM to bortezomib.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"9"},"PeriodicalIF":9.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine RNA modification regulates the transcription of SLC7A11 through KDM6B and GATA3 to modulate ferroptosis.","authors":"Haisheng Zhang, Cheng Yi, Jianing Li, Yunqing Lu, Haoran Wang, Lijun Tao, Jiawang Zhou, Yonghuang Tan, Jiexin Li, Zhuojia Chen, Gholamreza Asadikaram, Jie Cao, Jianxin Peng, Wanglin Li, Junming He, Hongsheng Wang","doi":"10.1186/s12929-024-01100-y","DOIUrl":"10.1186/s12929-024-01100-y","url":null,"abstract":"<p><strong>Background: </strong>Recent studies indicate that N6-methyladenosine (m⁶A) RNA modification may regulate ferroptosis in cancer cells, while its molecular mechanisms require further investigation.</p><p><strong>Methods: </strong>Liquid Chromatography-Tandem Mass Spectrometry (HPLC/MS/MS) was used to detect changes in m⁶A levels in cells. Transmission electron microscopy and flow cytometry were used to detect mitochondrial reactive oxygen species (ROS). RNA sequencing (RNA-seq) was employed to analyze the factors regulating ferroptosis. Chromatin immunoprecipitation (ChIP) was used to assess the binding of regulatory factors to the SLC7A11 promoter, and a Dual-Luciferase reporter assay measured promoter activity of SLC7A11. The dm⁶ACRISPR system was utilized for the demethylation of specific transcripts. The Cancer Genome Atlas Program (TCGA) database and immunohistochemistry validated the role of the METTL3/SLC7A11 axis in cancer progression.</p><p><strong>Results: </strong>The m⁶A methyltransferase METTL3 was upregulated during cancer cell ferroptosis and facilitated erastin-induced ferroptosis by enhancing mitochondrial ROS. Mechanistic studies showed that METTL3 negatively regulated the transcription and promoter activity of SLC7A11. Specifically, METTL3 induced H3K27 trimethylation of the SLC7A11 promoter by suppressing the mRNA stability of H3K27 demethylases KDM6B. Furthermore, METTL3 suppressed the expression of GATA3, which regulated SLC7A11 transcription by binding to the putative site at - 597 to - 590 of the SLC7A11 promoter. METTL3 decreased the precursor mRNA stability of GATA3 through m⁶A/YTHDF2-dependent recruitment of the 3'-5' exoribonuclease Dis3L2. Targeted demethylation of KDM6B and GATA3 m⁶A using the dm⁶ACRISPR system significantly increased the expression of SLC7A11. Moreover, the transcription factor YY1 was responsible for erastin-induced upregulation of METTL3 by binding to its promoter-proximal site. In vivo and clinical data supported the positive roles of the METTL3/SLC7A11 axis in tumor growth and progression.</p><p><strong>Conclusions: </strong>METTL3 regulated the transcription of SLC7A11 through GATA3 and KDM6B to modulate ferroptosis in an m⁶A-dependent manner. This study provides a novel potential strategy and experimental support for the future treatment of cancer.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"8"},"PeriodicalIF":9.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.","authors":"Zhipeng Cao, Sadia Quazi, Sakshi Arora, Laura D Osellame, Ingrid J Burvenich, Peter W Janes, Andrew M Scott","doi":"10.1186/s12929-024-01099-2","DOIUrl":"10.1186/s12929-024-01099-2","url":null,"abstract":"<p><p>Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"7"},"PeriodicalIF":9.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel human specific lncRNA MEK6-AS1 regulates adipogenesis and fatty acid biosynthesis by stabilizing MEK6 mRNA.","authors":"Di Li, Yunhua Chen, Xingyu Zhu, Yanlei Yang, Hongling Li, Robert Chunhua Zhao","doi":"10.1186/s12929-024-01098-3","DOIUrl":"https://doi.org/10.1186/s12929-024-01098-3","url":null,"abstract":"<p><strong>Background: </strong>Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective and safe clinical treatment strategies still need to be deeply explored. Increased number and volume of adipocytes lead to overweight and obesity. The aim of our work is to identify lncRNAs that have important regulatory in differentiation of human mesenchymal stem cells (MSCs) into adipocytes, and to provide effective targets for clinical prevention and treatment of obesity and related metabolic disorders.</p><p><strong>Methods: </strong>We extracted primary MSCs from human adipose tissue, and conducted expression profile analysis of lncRNAs during adipogenic differentiation of MSCs to screen changed lncRNAs. Characteristics of lncRNA were revealed mainly by RACE and RNA FISH. Loss- and gain-of function experiments in vivo and in vitro were used to analyze effects of lncRNA. Targeted metabolomics was utilized to detect levels of free fatty acids. RNA pull-down, mRNA stability tests, etc. were employed to explore mechanisms of lncRNA.</p><p><strong>Results: </strong>Human-specific lncRNA, we named it MEK6-AS1, was the most up-regulated transcript during adipogenic differentiation of MSCs. MEK6-AS1 was highly expressed in adipose tissue samples from individuals with BMI ≥ 25 and positively correlated with adipogenic marker genes in these samples. Knocking down lncRNA inhibited expression of adipogenic differentiation markers and ectopic adipogenesis, reducing contents of various free fatty acids, as well as promoting osteogenic differentiation. Overexpression of lncRNA had the opposite effects to the above processes. We also found that MEK6-AS1 was elevated during hepatic steatosis organoid generation. Mechanistically, MEK6-AS1 worked partially through stabilization of MEK6 mRNA by NAT10.</p><p><strong>Conclusions: </strong>We have identified a human-specific lncRNA (MEK6-AS1) with position information in the genomic database but has not been extensively reported. We demonstrated that MEK6-AS1 as a novel lncRNA involved in adipogenic differentiation and adipogenesis, fatty acid metabolism, and osteogenic differentiation. We found that MEK6-AS1 may exert its effect by enhancing MEK6 mRNA stability through NAT10. Our study may provide insights into implication of lncRNAs in stem cell biology and offer a new potential therapeutic target for the prevention and treatment of obesity and other related disease.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"6"},"PeriodicalIF":9.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition.","authors":"Yulong Yu, Han Yin, Bili Wu, Weiheng Zhao, Yuan Wang, Aifeina Aili, Mu Yang, Qianqian Yu, Xianglin Yuan","doi":"10.1186/s12929-024-01097-4","DOIUrl":"https://doi.org/10.1186/s12929-024-01097-4","url":null,"abstract":"<p><strong>Background: </strong>The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum (F. nucleatum, FN) being found in high abundance in colorectal cancer tissues. Previous research has emphasized the significant role of F. nucleatum in the occurrence of CRC. However, the impact of F. nucleatum on CRC liver metastasis has not been well understood.</p><p><strong>Methods: </strong>The effects of F. nucleatum on metastasis ability of CRC cell were evaluated in vitro were examined by wound-healing assay and transwell assay. The mouse model of CRC liver metastasis was constructed by spleen injection, and the degree of liver metastasis was assessed by in vivo bioluminescence imaging. The gene expression changes in CRC cells after co-culture with F. nucleatum was analyzed through transcriptome sequencing. qRT-PCR and Western Blot assays were performed to validate the expression of related genes and proteins.</p><p><strong>Results: </strong>The metastasis ability of CRC cells was significantly enhanced after co-culture with F. nucleatum in vitro. In the mouse model, F. nucleatum also promoted the development of liver metastasis in CRC. Mechanistically, F. nucleatum infection increased the expression of IL-8 by downregulated the level of miR-5692a, a regulatory microRNA of IL-8. This led to the activation of the ERK pathway and resulted in the epithelial-mesenchymal transition (EMT) of CRC cells.</p><p><strong>Conclusions: </strong>Our results suggest that F. nucleatum promotes CRC liver metastasis by inducing epithelial-mesenchymal transition through the miR-5692a/IL-8 axis. These findings provide new insights for the prevention and treatment of colorectal cancer liver metastasis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"5"},"PeriodicalIF":9.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of extracellular vesicles in the pathogenesis of mosquito-borne flaviviruses that impact public health.","authors":"Pedro Pablo Martínez-Rojas, Verónica Monroy-Martínez, Blanca H Ruiz-Ordaz","doi":"10.1186/s12929-024-01096-5","DOIUrl":"10.1186/s12929-024-01096-5","url":null,"abstract":"<p><p>Mosquito-borne flaviviruses represent a public health challenge due to the high-rate endemic infections, severe clinical outcomes, and the potential risk of emerging global outbreaks. Flavivirus disease pathogenesis converges on cellular factors from vectors and hosts, and their interactions are still unclear. Exosomes and microparticles are extracellular vesicles released from cells that mediate the intercellular communication necessary for maintaining homeostasis; however, they have been shown to be involved in disease establishment and progression. This review focuses on the roles of extracellular vesicles in the pathogenesis of mosquito-borne flavivirus diseases: how they contribute to viral cycle completion, cell-to-cell transmission, and cellular responses such as inflammation, immune suppression, and evasion, as well as their potential use as biomarkers or therapeutics (antiviral or vaccines). We highlight the current findings concerning the functionality of extracellular vesicles in different models of dengue virus, Zika virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus infections and diseases. The available evidence suggests that extracellular vesicles mediate diverse functions between hosts, constituting novel effectors for understanding the pathogenic mechanisms of flaviviral diseases.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"4"},"PeriodicalIF":9.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing the biomolecular relevance of cell culture practice.","authors":"Raluca E Ghebosu, Lawrence Hui, Joy Wolfram","doi":"10.1186/s12929-024-01095-6","DOIUrl":"10.1186/s12929-024-01095-6","url":null,"abstract":"<p><p>The biomolecular relevance of medium supplements is a key challenge affecting cell culture practice. The biomolecular composition of commonly used supplements differs from that of a physiological environment, affecting the validity of conclusions drawn from in vitro studies. This article discusses the advantages and disadvantages of common supplements, including context-dependent considerations for supplement selection to improve biomolecular relevance, especially in nanomedicine and extracellular vesicle research.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"3"},"PeriodicalIF":9.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBV DNA integration and somatic mutations in HCC patients with HBV-HCV dual infection reveals profiles intermediate between HBV- and HCV-related HCC.","authors":"Chiao-Ling Li, Chia-Lang Hsu, You-Yu Lin, Ming-Chih Ho, Rey-Heng Hu, Sheng-Tai Tzeng, Ya-Chun Wang, Yasuhito Tanaka, Pei-Jer Chen, Shiou-Hwei Yeh","doi":"10.1186/s12929-024-01094-7","DOIUrl":"10.1186/s12929-024-01094-7","url":null,"abstract":"<p><strong>Background: </strong>In regions with a high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, coinfected patients face a heightened risk of developing hepatocellular carcinoma (HCC), termed HBV/HCV-related HCC (HBCV-HCC). We aimed to investigate the contribution of preexisting chronic hepatitis B (CHB) and subsequent chronic hepatitis C (CHC) to the development of HBCV-HCC.</p><p><strong>Methods: </strong>We examined HBV's involvement in 93 HBCV-HCC cases by analyzing HBV DNA integration as an indicator of HCC originating from HBV-infected hepatocytes, compared with 164 HBV-HCCs and 56 HCV-HCCs as controls.</p><p><strong>Results: </strong>Next generation sequencing revealed that 55% of HBCV-HCCs exhibited clonal HBV integration, which falls between the rates observed in HBV-HCCs (88%) and HCV-HCCs (7%), with similar integration patterns to HBV-HCCs. Common HCC somatic mutation analysis indicated HCV superinfection in HBCV-HCCs correlated with increased mutation rates in the telomerase reverse transcriptase (TERT) promoter and beta-catenin genes. Transcriptome analysis showed a prevalence of replicating HCV over HBV in HBCV-HCCs, with preexisting HBV exerting a proliferative role. The comparison of clinical characteristics revealed similarities between HBCV-HCC and HCV-HCC patients, including later onset for HBCV-HCC, possibly due to HCV superinfection slowing carcinogenesis. Notably, HBCV-HCCs with the same driver mutation, HBV integration at the TERT promoter, tended to develop later and showed a better prognosis post-tumor resection than HBV-HCCs.</p><p><strong>Conclusions: </strong>Our findings shed light on the interplay between preexisting CHB and subsequent CHC in elevating the risk of HBCV-HCC. These insights are crucial for understanding viral etiology-specific carcinogenesis and guiding surveillance policies for HBCV-HCC post-antiviral therapy.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"2"},"PeriodicalIF":9.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis.","authors":"Jing Wang, Chunshuang Li, Jinling Han, Yaoyao Xue, Xu Zheng, Ruoxi Wang, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba","doi":"10.1186/s12929-024-01093-8","DOIUrl":"10.1186/s12929-024-01093-8","url":null,"abstract":"<p><p>ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome. The accumulation of genomic 8-oxoGua and the dysfunction of OGG1 is readily linked to mutagenesis, and subsequently aging-related diseases and tumorigenesis; however, the direct experimental evidence has long been lacking. Recently, a series of studies have shown that guanine oxidation in the genome has a conservative bias, with the tendency to occur in the regulatory regions, thus, 8-oxoGua is not only a lesion to be repaired, but also an epigenetic modification. In this regard, OGG1 is a specific reader of this base modification. Substrate recognition and/or excision by OGG1 can cause DNA conformation changes, affect chromatin modifications, thereby modulating the transcription of genes involved in a variety of cellular processes, including inflammation, cell proliferation, differentiation, and apoptosis. Thus, in addition to the potential mutagenicity, 8-oxoGua may contribute to tumor development and progression through the altered gene expression stemming from its epigenetic effects.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"1"},"PeriodicalIF":9.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11689541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}