Journal of Molecular Medicine-Jmm最新文献

{"title":"Constitutive expression of the deubiquitinating enzyme CYLD does not affect microglia phenotype or function in homeostasis and neuroinflammation.","authors":"Eva Schramm, Vanessa Becker, Ilaria Palagi, Melanie Müller, Thomas Rösler, Feyza Durak, Anna Ebering, Khalad Karram, Esther von Stebut, Michael J Schmeisser, Ari Waisman","doi":"10.1007/s00109-024-02489-7","DOIUrl":"https://doi.org/10.1007/s00109-024-02489-7","url":null,"abstract":"<p><p>The deubiquitinating enzyme CYLD negatively regulates NF-κB signaling by removing activating ubiquitin chains from several members of the NF-κB pathway. Thereby, CYLD is critical for the maintenance and differentiation of various immune cells. Despite the importance of the NF-κB pathway in microglia regulation, the role of CYLD in microglia has not been investigated so far. In this study, we investigated whether CYLD in microglia can protect against neuroinflammation using a newly generated conditional mouse strain (Rosa26-Cyld-tdTomato) that allows cell type-specific CYLD overexpression. Here, we show that overexpression of CYLD in microglia did not alter microglia numbers or microglia morphology in different brain regions. Additionally, CYLD overexpression did not modify the microglial response to LPS-induced neuroinflammation or the disease severity in experimental autoimmune encephalomyelitis (EAE). Finally, also immune cell infiltration into the CNS during EAE and under steady state conditions remained unaffected by microglial CYLD overexpression. Our findings suggest that CYLD overexpression does not alter microglial function, and thus does not represent a viable therapeutic strategy in neuroinflammatory conditions. This study highlights the complexity of ubiquitin-mediated signaling in neuroinflammation and the need for cell-type-specific investigations. The Rosa26-Cyld-tdTomato mouse model offers a valuable tool for studying CYLD's role across various tissues and cell types. KEY MESSAGES: Novel mouse strain for cell type-specific overexpression of the deubiquitinating enzyme CYLD. CYLD overexpression in microglia did not alter microglia numbers or morphology in the steady state. CYLD overexpression in microglia did not protect mice from LPS-induced neuroinflammation or EAE. CYLD overexpression in microglia did not influence their gene expression during neuroinflammation.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Endothelin-1 induces the transactivation of vascular endothelial growth factor receptor-3 and modulates cell migration and vasculogenic mimicry in melanoma cells.","authors":"Francesca Spinella, Valentina Caprara, Valeriana Di Castro, Laura Rosanò, Roberta Cianfrocca, Pier Giorgio Natali, Anna Bagnato","doi":"10.1007/s00109-024-02484-y","DOIUrl":"https://doi.org/10.1007/s00109-024-02484-y","url":null,"abstract":"","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-21-5p derived from endometrial stromal cells promotes angiogenesis by targeting TIMP3 in ovarian endometrial cysts.","authors":"Liyuan Sun, Yan Cheng, Jing Wang, Di Wu, Lin Yuan, Xiaoyu Wei, Yan Li, Jie Gao, Guangmei Zhang","doi":"10.1007/s00109-024-02483-z","DOIUrl":"https://doi.org/10.1007/s00109-024-02483-z","url":null,"abstract":"<p><p>Endometriosis is a multifactorial gynecological disease, with angiogenesis as a key hallmark. The role of exosomal microRNAs (miRNAs) in endometriosis is not well understood. This study investigates differentially expressed exosomal miRNAs linked to angiogenesis in endometriosis, clarifies their molecular mechanisms, and identifies potential targets. Primary endometrial stromal cells (ESCs) were cultured, and exosomes were extracted. In a co-culture system, ESC-derived exosomes were taken up by human umbilical vein endothelial cells (HUVECs). Endometriosis implant-ESC-derived exosomes (EI-EXOs) significantly promoted HUVEC proliferation, migration and tube formation compared to normal endometrium-exosomes (NE-EXOs), a finding consistent in vivo in mice. MiRNA sequencing and bioinformatics identified differentially expressed miR-21-5p from EI-EXOs, confirmed by RT-qPCR. The miR-21-5p inhibitor or GW4869 attenuated EI-EXO-induced HUVEC proliferation, migration, and tube formation. TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, which was reversed by adding EI-EXOs or upregulating miR-21-5p. These findings validate the crosstalk between ESCs and HUVECs mediated by exosomal miR-21-5p, and confirm the miR-21-5p-TIMP3 axis in promoting angiogenesis in endometriosis. KEY MESSAGES: ESC-derived exosomes were found to be taken up by recipient cells, i.e. HUVECs. Functionally, endometriosis implant-ESC-derived exosomes (EI-EXOs) could significantly promote the proliferation, migration and tube formation of HUVECs compared to normal endometrium-exosomes (NE-EXOs). Through miRNA sequencing and bioinformatics analysis, differentially expressed miR-21-5p released by EI-EXOs was chosen, as confirmed by qRT-PCR. miR-21-5p inhibitor or GW4869 was found to attenuate the proliferation, migration, and tube formation of HUVECs induced by EI-EXOs. In turn, TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, and this angiogenic phenotype was reversed once EI-EXOs were added or miR-21-5p was upregulated.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic profiles in blood and adipose tissue: identifying strong correlations in morbidly obese and non-obese patients.","authors":"Antonio Cantarero-Cuenca, Andres Gonzalez-Jimenez, Gracia M Martínez-Núñez, Lourdes Garrido-Sánchez, Juan A G Ranea, Francisco J Tinahones","doi":"10.1007/s00109-024-02475-z","DOIUrl":"https://doi.org/10.1007/s00109-024-02475-z","url":null,"abstract":"<p><p>Epigenetic alterations play a pivotal role in conditions influenced by environmental factors such as overweight and obesity. Many of these changes are tissue-specific, which entails a problem in its study since obtaining human tissue is a complex and invasive practice. While blood is widely used as a surrogate biomarker, it cannot directly extrapolate the evidence found in blood to tissue. Moreover, the intricacies of metabolic diseases add a new layer of complexity, as obesity leads to significant alterations in adipose tissue, potentially causing associated pathologies that can disrupt existing correlations seen in healthy individuals. Here, our objective was to determine which epigenetic markers exhibit correlations between blood and adipose tissue, regardless of the metabolic status. We collected paired blood and adipose tissue samples from 64 patients with morbidity obesity and non-obese and employed the MethylationEPIC 850 K array for analysis. We found that only a small fraction, specifically 4.3% (corresponding to 34,825 CpG sites), of the sites showed statistically significant correlations (R ≥ 0.6) between blood and adipose tissue. Within this subset, 5327 CpG sites exhibited a strong correlation (R ≥ 0.8) between blood and adipose tissue. Our findings suggest that the majority of epigenetic markers in peripheral blood do not reliably reflect changes occurring in visceral adipose tissues. However, it is important to note that there exists a distinct set of epigenetic markers that can indeed mirror changes in adipose tissue within blood samples. KEY MESSAGES: More than 8% of methylation sites exhibit similarity between blood and adipose tissues, regardless of BMI The correlation percentage between blood and adipose tissue is strongly influenced by gender The principal genes implicated in this correlation are related to metabolism or the immunological system.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular targets in bone cancer pain: a systematic review of inflammatory cytokines.","authors":"Jacinta Ruivo, Isaura Tavares, Daniel H Pozza","doi":"10.1007/s00109-024-02464-2","DOIUrl":"10.1007/s00109-024-02464-2","url":null,"abstract":"<p><p>Bone cancer pain (BCP) profoundly impacts patient's quality of life, demanding more effective pain management strategies. The aim of this systematic review was to investigate the role of inflammatory cytokines as potential molecular targets in BCP. A systematic search for animal rodent models of bone cancer pain studies was conducted in PubMed, Scopus, and Web of Science. Methodological quality and risk of bias were assessed using the SYRCLE RoB tool. Twenty-five articles met the inclusion criteria, comprising animal studies investigating molecular targets related to inflammatory cytokines in BCP. A low to moderate risk of bias was reported. Key findings in 23 manuscripts revealed upregulated classic pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-18, IL-33) and chemokines in the spinal cord, periaqueductal gray, and dorsal root ganglia. Interventions targeting these cytokines consistently mitigated pain behaviors. Additionally, it was demonstrated that glial cells, due to their involvement in the release of inflammatory cytokines, emerged as significant contributors to BCP. This systematic review underscores the significance of inflammatory cytokines as potential molecular targets for alleviating BCP. It emphasizes the promise of targeted interventions and advocates for further research to translate these findings into effective therapeutic strategies. Ultimately, this approach holds the potential to enhance the patient's quality of life.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-based humanization of a therapeutic antibody for multiple myeloma.","authors":"Stephen F Marino, Oliver Daumke","doi":"10.1007/s00109-024-02470-4","DOIUrl":"10.1007/s00109-024-02470-4","url":null,"abstract":"<p><p>The optimal efficacy of xenogeneically generated proteins intended for application in humans requires that their own antigenicity be minimized. This necessary adaptation of antibodies to a humanized version poses challenges since modifications even distant from the binding sites can greatly influence antigen recognition and this is the primary feature that must be maintained during all modifications. Current strategies often rely on grafting and/or randomization/selection to arrive at a humanized variant retaining the binding properties of the original molecule. However, in terms of speed and efficiency, rationally directed approaches can be superior, provided the requisite structural information is available. We present here a humanization procedure based on the high-resolution X-ray structure of a chimaeric IgG against a marker for multiple myeloma. Based on in silico modelling of humanizing amino acid substitutions identified from sequence alignments, we devised a straightforward cloning procedure to rapidly evaluate the proposed sequence changes. Careful inspection of the structure allowed the identification of a potentially problematic amino acid change that indeed disrupted antigen binding. Subsequent optimization of the antigen binding loop sequences resulted in substantial recovery of binding affinity lost in the completely humanized antibody. X-ray structures of the humanized and optimized variants demonstrate that the antigen binding mode is preserved, with surprisingly few direct contacts to antibody atoms. These results underline the importance of structural information for the efficient optimization of protein therapeutics. KEY MESSAGES: Structure-based humanization of an IgG against BCMA, a marker for Multiple Myeloma. Identification of problematic mutations and unexpected modification sites. Structures of the modified IgG-antigen complexes verified predictions. Provision of humanized high-affinity IgGs against BCMA for therapeutic applications.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin improves cognitive dysfunction through SIRT1/NLRP3 pathway-mediated neuroinflammation in db/db mice.","authors":"Tian Hu, Jun-Wen Wei, Jia-Yi Zheng, Qing-Yi Luo, Xin-Rui Hu, Qun Du, Ye-Feng Cai, Shi-Jie Zhang","doi":"10.1007/s00109-024-02465-1","DOIUrl":"10.1007/s00109-024-02465-1","url":null,"abstract":"<p><p>Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1β, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-secreted S100A8/A9 participates in fatty liver injury and fibrosis by promoting myofibroblast migration.","authors":"Na Chang, Yuran Liu, Weiyang Li, Yuehan Ma, Xuan Zhou, Xinhao Zhao, Lin Yang, Liying Li","doi":"10.1007/s00109-024-02469-x","DOIUrl":"10.1007/s00109-024-02469-x","url":null,"abstract":"<p><p>Fatty liver, which is induced by abnormal lipid metabolism, is one of the most common causes of chronic liver disease globally and causes liver fibrosis. During this process, bone marrow-derived mesenchymal stromal cells (BMSCs) and hepatic stellate cells (HSCs) migrate toward the injured liver and participate in fibrogenesis by transdifferentiating into myofibroblasts. S100A8/A9 is a powerful inducer of cell migration and is involved in liver injury. But there are few reports about the effects of S100A8/A9 on BMSC/HSC migration. In the current study, we found that S100A8/A9 expression was increased during fatty liver injury/fibrogenesis. Moreover, S100A8/A9 expression had a positive correlation with fibrosis marker gene expressions in the injured liver. S100A8/A9 was mainly produced by neutrophils in the fibrotic liver. In vitro, neutrophil-secreted S100A8/A9 promoted BMSC/HSC migration via remodeling of microfilaments. Using specific siRNA and inhibitor, we proved that S100A8/A9-induced BMSC/HSC migration is dependent on TLR4/Rho GTPases signaling. Moreover, S100A8/A9 knock-down alleviated liver injury and fibrogenesis in vivo, while injection of S100A9 neutralizing antibody performed similar roles. We proved that S100A8/A9 was involved in liver injury and fibrogenesis via inducing BMSC/HSC migration. Our research reveals a new mechanism underlying BMSC/HSC migration in liver fibrosis and suggests S100A8/A9 as a potential therapeutic target of liver fibrosis. KEY MESSAGES: S100A8/A9 is secreted by neutrophils and increased in fatty liver injury. Neutrophil-secreted S100A8/A9 is a mediator of BMSC/HSC migration in vitro. S100A8/A9-induced BMSC/HSC migration is dependent on TLR4/Rho GTPases signaling. S100A8/A9 blockade alleviates liver injury and fibrogenesis in vivo.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of α7 nAChR-autophagy axis of deciduous tooth pulp stem cells in regulating IL-1β in the process of physiological root resorption of deciduous teeth.","authors":"Tiankai Di, Yujiang Chen, Zhifei Zhou, Jiajia Liu, Yang Du, Chao Feng, Bin Zhu, Lulu Wang","doi":"10.1007/s00109-024-02466-0","DOIUrl":"10.1007/s00109-024-02466-0","url":null,"abstract":"<p><p>Physiological root resorption of deciduous teeth is a normal phenomenon occurring during the developmental stages of children. Previous research has indicated the pivotal role of the inflammatory microenvironment in this process, although the specific mechanisms remain unclear. This study is aimed at elucidating the involvement of the alpha7 nicotinic acetylcholine receptors (α7 nAChR)-autophagy axis in the regulation of the inflammatory microenvironment during physiological root resorption in deciduous teeth. Samples were collected from deciduous teeth at various stages of physiological root resorption, and deciduous dental pulp stem cells (DDPSCs) were isolated and cultured during the mid-phase of root resorption. The findings revealed a substantial infiltration of the pulp of deciduous teeth at the mid-phase of root resorption, characterized by elevated expression levels of α7 nAChR and IL-1β. Significantly increased IL-1β and α7 nAChR expressions were observed in DDPSCs during the mid-phase of root resorption, with α7 nAChR demonstrating a regulatory effect on IL-1β. Moreover, evidence suggested that mechanical stress may act as a trigger, regulating autophagy and IL-1 expression via α7 nAChR. In conclusion, mechanical stress was identified as a regulator of autophagy in DDPSCs through α7 nAChR, influencing the expression of IL-1β and contributing to the formation of the inflammatory microenvironment. This mechanism plays a crucial role in the physiological root resorption of deciduous teeth. KEY MESSAGES: The pulp of deciduous teeth at mid-phase of root resorption was heavily infiltrated with high expression of α7nAChR and IL-1β. α7 nAChR acts as an initiating factor to regulate IL-1β through autophagy in DDPSCs. Mechanical stress can regulate autophagy of DDPSCs through α7 nAChR and thus affect IL-1β expression and inflammatory microenvironment formation in physiological root resorption in deciduous teeth.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs role in telomere length maintenance and telomerase activity in tumor cells.","authors":"Stéfanne Bortoletto, Emanuelle Nunes-Souza, Rafael Marchi, Mayara Oliveira Ruthes, Larissa M Okano, Maria Vitoria Tofolo, Ariana Centa, Aline S Fonseca, Daiane Rosolen, Luciane R Cavalli","doi":"10.1007/s00109-024-02467-z","DOIUrl":"10.1007/s00109-024-02467-z","url":null,"abstract":"<p><p>MiRNAs, a class of non-coding RNA molecules, have emerged as critical modulators of telomere length and telomerase activity by finely tuning the expression of target genes (and not gene targets) within signaling pathways involved in telomere homeostasis. The primary objective of this systematic review was to compile and synthesize the existing body of knowledge on the role, association, and involvement of miRNAs in telomere length. Additionally, the review explored the regulation, function, and activation mechanism of the human telomerase reverse transcriptase (hTERT) gene and telomerase activity in tumor cells. A comprehensive analysis of 47 selected articles revealed 40 distinct miRNAs involved in these processes. These miRNAs were shown to exert their function, in both clinical cases and cell line models, either directly or indirectly, regulating hTERT and telomerase activity through distinct molecular mechanisms. The regulatory roles of these miRNAs significantly affected major cancer phenotypes, with outcomes largely dependent on the tissue type and the cellular actions within the tumor cells, whereby they functioned as oncogenes or tumor suppressors. These findings strongly support the pivotal role of miRNAs in modulating telomere length and telomerase activity, thereby contributing to the intricate and complex regulation of telomere homeostasis in tumor cells. Moreover, they emphasize the potential of targeting miRNAs and key regulatory genes as therapeutic strategies to disrupt cancer cell growth and promote senescence, offering promising avenues for novel cancer treatments.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}