Cell Biology and Toxicology最新文献

{"title":"EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.","authors":"Xun Zhang, Yan Bian, Qiuxin Li, Chuting Yu, Ye Gao, Bo Tian, Wenqiang Xia, Wei Wang, Lei Xin, Han Lin, Luowei Wang","doi":"10.1007/s10565-024-09927-9","DOIUrl":"10.1007/s10565-024-09927-9","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"84"},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388331","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":"S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition.","authors":"Xuejia Yang, Fan Zheng, Penghua Yan, Xueting Liu, Xuanwen Chen, Xinyu Du, Yin Zhang, Peilei Wang, Chaosheng Chen, Hong Lu, Yongheng Bai","doi":"10.1007/s10565-024-09929-7","DOIUrl":"10.1007/s10565-024-09929-7","url":null,"abstract":"<p><strong>Background: </strong>Renal interstitial fibrosis (RIF) is a common feature of chronic kidney diseases (CKD), with epithelial-mesenchymal transition (EMT) being one of its important mechanisms. S100A2 is a protein associated with cell proliferation and differentiation, but its specific functions and molecular mechanisms in RIF remain to be determined.</p><p><strong>Methods: </strong>S100A2 levels were evaluated in three mouse models, including unilateral ureteral obstruction (UUO), ischemia-reperfusion injury (IRI), and aristolochic acid nephropathy (AAN), as well as in TGF-β1- treated HK-2 cells and in kidney tissue samples. Furthermore, the role of S100A2 and its interaction with FoxO1 was investigated using RT-qPCR, immunoblotting, immunofluorescence staining, co-immunoprecipitation (Co-IP), transcriptome sequencing, and gain- or loss-of-function approaches in vitro.</p><p><strong>Results: </strong>Elevated expression levels of S100A2 were observed in three mouse models and TGF-β1-treated HK2 cells, as well as in kidney tissue samples. Following siRNA silencing of S100A2, exposure to TGF-β1 in cultured HK-2 cells suppressed EMT process and extracellular matrix (ECM) accumulation. Conversely, Overexpression of S100A2 induced EMT and ECM deposition. Notably, we identified that S100A2-mediated EMT depends on FoxO1. Immunofluorescence staining indicated that S100A2 and FoxO1 colocalized in the nucleus and cytoplasm, and their interaction was verified in Co-IP assay. S100A2 knockdown decreased TGF-β1-induced phosphorylation of FoxO1 and increased its protein expression, whereas S100A2 overexpression hampered FoxO1 activation. Furthermore, pharmacological blockade of FoxO1 rescued the induction of TGF-β1 on EMT and ECM deposition in S100A2 siRNA-treated cells.</p><p><strong>Conclusion: </strong>S100A2 activation exacerbates interstitial fibrosis in kidneys by facilitating FoxO1-mediated EMT.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"86"},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388334","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":"Exogenous and endogenous formaldehyde-induced DNA damage in the aging brain: mechanisms and implications for brain diseases.","authors":"Zixi Tian, Kai Huang, Wanting Yang, Ying Chen, Wanjia Lyv, Beilei Zhu, Xu Yang, Ping Ma, Zhiqian Tong","doi":"10.1007/s10565-024-09926-w","DOIUrl":"10.1007/s10565-024-09926-w","url":null,"abstract":"<p><p>Exogenous gaseous formaldehyde (FA) is recognized as a significant indoor air pollutant due to its chemical reactivity and documented mutagenic and carcinogenic properties, particularly in its capacity to damage DNA and impact human health. Despite increasing attention on the adverse effects of exogenous FA on human health, the potential detrimental effects of endogenous FA in the brain have been largely neglected in current research. Endogenous FA have been observed to accumulate in the aging brain due to dysregulation in the expression and activity of enzymes involved in FA metabolism. Surprisingly, excessive FA have been implicated in the development of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancers. Notably, FA has the ability to not only initiate DNA double strand breaks but also induce the formation of crosslinks of DNA-DNA, DNA-RNA, and DNA-protein, which further exacerbate the progression of these brain diseases. However, recent research has identified that FA-resistant gene exonuclease-1 (EXO1) and FA scavengers can potentially mitigate FA toxicity, offering a promising strategy for mitigating or repairing FA-induced DNA damage. The present review offers novel insights into the impact of FA metabolism on brain ageing and the contribution of FA-damaged DNA to the progression of neurological disorders.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"83"},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375137","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":"ACE2 alleviates sepsis-induced cardiomyopathy through inhibiting M1 macrophage via NF-κB/STAT1 signals.","authors":"Xue Xiao, Jia-Xin Li, Hui-Hua Li, Fei Teng","doi":"10.1007/s10565-024-09923-z","DOIUrl":"10.1007/s10565-024-09923-z","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2), a crucial element of the renin-angiotensin system (RAS), metabolizes angiotensin II into Ang (1-7), which then combines with the Mas receptor (MasR) to fulfill its protective role in various diseases. Nevertheless, the involvement of ACE2 in sepsis-induced cardiomyopathy (SIC) is still unexplored. In this study, our results revealed that CLP surgery dramatically impaired cardiac function accompanied with disruption of the balance between ACE2-Ang (1-7) and ACE-Ang II axis in septic heart tissues. Moreover, ACE2 knockin markedly alleviated sepsis induced RAS disorder, cardiac dysfunction and improved survival rate in mice, while ACE2 knockout significantly exacerbates these outcomes. Adoptive transfer of bone marrow cells and in vitro experiments showed the positive role of myeloid ACE2 by mitigating oxidative stress, inflammatory response, macrophage polarization and cardiomyocyte apoptosis by blocking NF-κB and STAT1 signals. However, the beneficial impacts were nullified by MasR antagonist A779. Collectively, these findings showed that ACE2 alleviated SIC by inhibiting M1 macrophage via activating the Ang (1-7)-MasR axis, highlight that ACE2 might be a promising target for the management of sepsis and SIC patients.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"82"},"PeriodicalIF":5.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342289","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":"Neddylation signaling inactivation by tetracaine hydrochloride suppresses cell proliferation and alleviates vemurafenib-resistance of melanoma.","authors":"Xiang Huang, Peng Yi, Wanrong Gou, Ran Zhang, Chunlin Wu, Li Liu, Yijing He, Xian Jiang, Jianguo Feng","doi":"10.1007/s10565-024-09916-y","DOIUrl":"10.1007/s10565-024-09916-y","url":null,"abstract":"<p><p>Tetracaine, a local anesthetic, exhibits potent cytotoxic effects on multiple cancer; however, the precise underlying mechanisms of its anti-cancer activity remain uncertain. The anti-cancer activity of tetracaine was found to be the most effective among commonly used local anesthetics in this study. After tetracaine treatment, the differentially expressed genes in melanoma cells were identified by the RNAseq technique and enriched in the lysosome signaling pathway, cullin family protein binding, and proteasome signaling pathway through Kyoto Encyclopedia of Genes and Genomes. Additionally, the ubiquitin-like neddylation signaling pathway, which is hyperactivated in melanoma, could be abrogated due to decreased NAE2 expression after tetracaine treatment. The neddylation of the pro-oncogenic Survivin, which enhances its stability, was significantly reduced following treatment with tetracaine. The activation of neddylation signaling by NEDD8 overexpression could reduce the antitumor efficacy of tetracaine in vivo and in vitro. Furthermore, vemurafenib-resistant melanoma cells showed higher level of neddylation, and potential substrate proteins undergoing neddylation modification were identified through immunoprecipitation and mass spectrometry. The tetracaine treatment could reduce drug resistance via neddylation signaling pathway inactivation in melanoma cells. These findings demonstrate that tetracaine effectively inhibits cell proliferation and alleviates vemurafenib resistance in melanoma by suppressing the neddylation signaling pathway, providing a promising avenue for controlling cancer progression.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"81"},"PeriodicalIF":5.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280721","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":"The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress","authors":"Yihong Jiang, Zeyu Zheng, Jing Zhu, Peng Zhang, Shaoheng Li, Yang Fu, Fei Wang, Zhuoru Zhang, Tong Chang, Min Zhang, Bai Ruan, Xiaocheng Wang","doi":"10.1007/s10565-024-09912-2","DOIUrl":"https://doi.org/10.1007/s10565-024-09912-2","url":null,"abstract":"<p>Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3><ol>\u0000<li>\u0000<span>1.</span>\u0000<p>HHL mice had a transient threshold shift, reduced ABR wave I amplitude, and decreased number of ribbon synapses.</p>\u0000</li>\u0000<li>\u0000<span>2.</span>\u0000<p>HHL mice's cochlear hair cells exhibited increased oxidative stress and elevated GDF15 expression.</p>\u0000</li>\u0000<li>\u0000<span>3.</span>\u0000<p>Upregulation of GDF15 attenuated oxidative stress and auditory damage in the cochlea of HHL mice, implying that GDF15-targeted treatment techniques may be useful for HHL.</p>\u0000</li>\u0000</ol>\u0000","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"24 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265168","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":"Hepsin as a potential therapeutic target for alleviating acetaminophen-induced hepatotoxicity via gap-junction regulation and oxidative stress modulation","authors":"Yu-Fei Tsai, Chien-Hung Chen, Yao-Ming Wu, Chia-Lu Hung, Mo-Chu Fang, I.-Shing Yu, Jin-Chuan Sheu, Yu-Chen Hsu, Shu-Wha Lin","doi":"10.1007/s10565-024-09915-z","DOIUrl":"https://doi.org/10.1007/s10565-024-09915-z","url":null,"abstract":"<p>Acetaminophen (APAP) overdose is a leading cause of drug-induced liver damage, highlighting the limitations of current emergency treatments that primarily involve administering the glutathione precursor N-acetylcysteine and supportive therapy. This study highlights the essential protective role of the type II transmembrane serine protease (TTSP), hepsin, in mitigating acetaminophen-induced liver injury, particularly through its regulation of gap junction (GJ) abundance in response to reactive oxygen stress in the liver. We previously reported that reduced levels of activated hepatocyte growth factor and the c-Met receptor tyrosine kinase—both of which are vital for maintaining cellular redox balance—combined with increased expression of GJ proteins in hepsin-deficient mice. Here, we show that hepsin deficiency in mice exacerbates acetaminophen toxicity compared to wild-type mice, leading to more severe liver pathology, elevated oxidative stress, and greater mortality within 6 h after exposure. Administering hepsin had a protective effect in both mouse models, reducing hepatotoxicity by modulating GJ abundance. Additionally, transcriptome analysis and a functional GJ inhibitor have highlighted hepsin's mechanism for managing oxidative stress. Combining hepsin with relatively low doses of N-acetylcysteine had a synergistic effect that was more efficacious than high-dose N-acetylcysteine alone. Our results illustrate the crucial role of hepsin in modulating the abundance of hepatic GJs and reducing oxidative stress, thereby offering early protection against acetaminophen-induced hepatotoxicity and a new, combination approach. Emerging as a promising therapeutic target, hepsin holds potential for combination therapy with N-acetylcysteine, paving the way for novel approaches in managing drug-induced liver injury.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3><p>1. Hepsin−/− mice exhibit exacerbated APAP toxicity, resulting in more severe liver damage, elevated oxidative stress, and higher mortality.</p><p>2. Hepsin is crucial in protecting against APAP-induced liver injury by regulating gap junctions and reducing oxidative stress.</p><p>3. Combining hepsin with low doses of N-acetylcysteine provides greater protection against APAP-induced hepatotoxicity than high-dose NAC alone.</p>\u0000","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"74 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265170","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":"TRMT10C-mediated m7G modification of circFAM126A inhibits lung cancer growth by regulating cellular glycolysis","authors":"Qingyun Zhao, Xiaofei Li, Jiaxi Wu, Ruirui Zhang, Sixian Chen, Dunyu Cai, Haotian Xu, Wenyi Peng, Gang Li, Aruo Nan","doi":"10.1007/s10565-024-09918-w","DOIUrl":"https://doi.org/10.1007/s10565-024-09918-w","url":null,"abstract":"<p>The N⁷-methylguanosine (m7G) modification and circular RNAs (circRNAs) have been shown to play important roles in the development of lung cancer. However, the m7G modification of circRNAs has not been fully elucidated. This study revealed the presence of the m7G modification in circFAM126A. We propose the novel hypothesis that the methyltransferase TRMT10C mediates the m7G modification of circFAM126A and that the stability of m7G-modified circFAM126A is reduced. circFAM126A is downregulated in lung cancer and significantly inhibits lung cancer growth both in vitro and in vivo. The expression of circFAM126A correlates with the stage of lung cancer and with the tumour diameter, and circFAM126A can be used as a potential molecular target for lung cancer. The molecular mechanism by which circFAM126A increases HSP90 ubiquitination and suppresses AKT1 expression to regulate cellular glycolysis, ultimately inhibiting the progression of lung cancer, is elucidated. This study not only broadens the knowledge regarding the expression and regulatory mode of circRNAs but also provides new insights into the molecular mechanisms that regulate tumour cell metabolism and affect tumour cell fate from an epigenetic perspective. These findings will facilitate the development of new strategies for lung cancer prevention and treatment.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3><p>Graphical Headlights</p><p>• circRNA can undergo m7G modification. The methyltransferase TRMT10C mediates circFAM126A m7G modification, thereby enhancing circFAM126A stability.</p><p>• m7G-modified circFAM126A can perform a biological function in inhibiting lung cancer progression by regulating cellular glycolysis.</p><p>• circFAM126A increases ubiquitination of HSP90 and inhibits AKT1 expression to regulate cellular glycolysis.</p>\u0000","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"101 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265167","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":"MicroRNA-155 and its exosomal form: Small pieces in the gastrointestinal cancers puzzle","authors":"Jinbao Guo, Li Zhong, Mohammad Reza Momeni","doi":"10.1007/s10565-024-09920-2","DOIUrl":"https://doi.org/10.1007/s10565-024-09920-2","url":null,"abstract":"<p>Gastrointestinal (GI) cancers are common cancers that are responsible for a large portion of global cancer fatalities. Due to this, there is a pressing need for innovative strategies to identify and treat GI cancers. MicroRNAs (miRNAs) are short ncRNAs that can be considered either cancer-causing or tumor-inhibiting molecules. MicroRNA-155, also known as miR-155, is a vital regulator in various cancer types. This miRNA has a carcinogenic role in a variety of gastrointestinal cancers, including pancreatic, colon, and gastric cancers. Since the abnormal production of miR-155 has been detected in various malignancies and has a correlation with increased mortality, it is a promising target for future therapeutic approaches. Moreover, exosomal miR-155 associated with tumors have significant functions in communicating between cells and establishing the microenvironment for cancer in GI cancers. Various types of genetic material, such as specifically miR-155 as well as proteins found in cancer-related exosomes, have the ability to be transmitted to other cells and have a function in the advancement of tumor. Therefore, it is critical to conduct a review that outlines the diverse functions of miR-155 in gastrointestinal malignancies. As a result, we present a current overview of the role of miR-155 in gastrointestinal cancers. Our research highlighted the role of miR-155 in GI cancers and covered critical issues in GI cancer such as pharmacologic inhibitors of miRNA-155, miRNA-155-assosiated circular RNAs, immune-related cells contain miRNA-155. Importantly, we discussed miRNA-155 in GI cancer resistance to chemotherapy, diagnosis and clinical trials. Furthermore, the function of miR-155 enclosed in exosomes that are released by cancer cells or tumor-associated macrophages is also covered.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3><p>Various mechanisms can be affected by miNA-155 and exosomal miR-155. Various molecular processes linked to angiogenesis and apoptosis in GI cancers.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"44 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265410","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":"tRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease","authors":"Di Wu, Xiuling Li, Faheem Ahmed Khan, Chenyang Yuan, Nuruliarizki Shinta Pandupuspitasari, Chunjie Huang, Fei Sun, Kaifeng Guan","doi":"10.1007/s10565-024-09919-9","DOIUrl":"https://doi.org/10.1007/s10565-024-09919-9","url":null,"abstract":"<p>tRNAs are codon decoders that convert the transcriptome into the proteome. The field of tRNA research is excited by the increasing discovery of specific tRNA modifications that are installed at specific, evolutionarily conserved positions by a set of specialized tRNA-modifying enzymes and the biogenesis of tRNA-derived regulatory fragments (tsRNAs) which exhibit copious activities through multiple mechanisms. Dysregulation of tRNA modification usually has pathological consequences, a phenomenon referred to as \"tRNA modopathy\". Current evidence suggests that certain tRNA-modifying enzymes and tsRNAs may serve as promising diagnostic biomarkers and therapeutic targets, particularly for chemoresistant cancers. In this review, we discuss the latest discoveries that elucidate the molecular mechanisms underlying the functions of clinically relevant tRNA modifications and tsRNAs, with a focus on malignancies. We also discuss the therapeutic potential of tRNA/tsRNA-based therapies, aiming to provide insights for the development of innovative therapeutic strategies. Further efforts to unravel the complexities inherent in tRNA biology hold the promise of yielding better biomarkers for the diagnosis and prognosis of diseases, thereby advancing the development of precision medicine for health improvement.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"31 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265169","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}