International Journal of Biological Sciences最新文献_第8页

The Mechanism and Latest Progress of m6A Methylation in the Progression of Pancreatic Cancer.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104407

Ze-Hao Liu, Peng Ma, Ying He, Yue-Feng Zhang, Zuo Mou, Ting Fang, Wei Wang, Kai-Huan Yu

{"title":"The Mechanism and Latest Progress of m6A Methylation in the Progression of Pancreatic Cancer.","authors":"Ze-Hao Liu, Peng Ma, Ying He, Yue-Feng Zhang, Zuo Mou, Ting Fang, Wei Wang, Kai-Huan Yu","doi":"10.7150/ijbs.104407","DOIUrl":"10.7150/ijbs.104407","url":null,"abstract":"Pancreatic cancer (PC), known as the \"king of cancers,\" is characterized by an exceptionally low five-year survival rate, posing a formidable challenge to global public health. N6-methyladenosine (m6A) methylation is prevalent across various stages of eukaryotic RNA expression, including splicing, maturation, stability, translation, and localization, and represents a pivotal mechanism of epigenetic regulation. m6A methylation influences tumor initiation and progression by modulating post-transcriptional processes, playing a critical role in sustaining cancer cell stemness, promoting cell proliferation, and mediating drug resistance. Extensive research underscores the substantial contribution of m6A modifications to PC development. However, the multiplicity of m6A regulators and their intricate mechanisms of action complicate the landscape. This review aims to deepen the understanding of m6A's role in PC by delineating its involvement in four key areas of tumorigenesis: the hypoxic tumor microenvironment, metabolic reprogramming, immune microenvironment, and resistance mechanisms. Additionally, the review addresses the emerging frontier of m6A interactions with non-coding RNAs (ncRNAs), offering insights into the potential therapeutic and prognostic applications of m6A in the treatment and prognosis prediction of PC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1187-1201"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FOXM1-Driven CKS1B Upregulation Promotes Pancreatic Cancer Progression and Therapeutic Resistance.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105289

Liuxi Zhang, Fang Wei, Qihui Sun, Xinyan Huang, Qi Zou, Mengmeng Jiang, Yuling Su, Shu Li, Xiaojia Li, Keping Xie, Jie He

{"title":"FOXM1-Driven CKS1B Upregulation Promotes Pancreatic Cancer Progression and Therapeutic Resistance.","authors":"Liuxi Zhang, Fang Wei, Qihui Sun, Xinyan Huang, Qi Zou, Mengmeng Jiang, Yuling Su, Shu Li, Xiaojia Li, Keping Xie, Jie He","doi":"10.7150/ijbs.105289","DOIUrl":"10.7150/ijbs.105289","url":null,"abstract":"Background: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited treatment options. Investigating novel therapeutic targets and understanding mechanisms of chemoresistance are crucial for improving patient outcomes. This study investigated the role of CKS1B in PDAC carcinogenesis, stemness and chemoresistance, and explores the underlying mechanisms driving its upregulation. The findings may provide novel therapeutic insights and potential strategies for the treatment of PDAC. Methods: CKS1B expression was analyzed in PDAC tissues and cell lines, its impact on cell proliferation, migration, apoptosis, stemness and chemosensitivity were evaluated by using in vitro and in vivo models, and its underlying mechanistic connection to transcription factor FOXM1 was explored by using molecular biology methods. Results: CKS1B was significantly upregulated in PDAC tissues and correlated with poor patient survival. CKS1B promoted PDAC cell proliferation, migration, and inhibited apoptosis. Expression of CKS1B enhanced the stemness properties of pancreatic cancer. CKS1B knockdown sensitized PDAC cells to the treatment of gemcitabine and oxaliplatin. Mechanistically, CKS1B is transcriptionally regulated by FOXM1, establishing a novel FOXM1-CKS1B signaling axis that regulates carcinogenesis, proliferation, migration, stemness, apoptosis, and drug resistance in PDAC. Conclusions: Our findings strongly suggest that CKS1B plays a critical role in PDAC progression, stemness and chemoresistance. Targeting the FOXM1-CKS1B axis represents a promising therapeutic strategy for PDAC patients.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1047-1064"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.102776

Xiaobo Wang, Bingyu Wang, Jiawei Shi, Zefu Chen, Yongpei Wu, Jingmin Liu, Zhongmin Zhang, Yang Wang, Jia Dan, Xin Zheng

{"title":"GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3.","authors":"Xiaobo Wang, Bingyu Wang, Jiawei Shi, Zefu Chen, Yongpei Wu, Jingmin Liu, Zhongmin Zhang, Yang Wang, Jia Dan, Xin Zheng","doi":"10.7150/ijbs.102776","DOIUrl":"10.7150/ijbs.102776","url":null,"abstract":"This study explored the role of ferroptosis in intervertebral disc degeneration (IVDD), and identified GATA6 as a key regulator of this process. A ferroptosis-related gene risk coefficient model was constructed using differential gene expression analysis of the GSE70362 dataset. The analysis identified GATA6 as a significant factor in IVDD progression. GATA6 was shown to promote ferroptosis in nucleus pulposus cells (NPCs) by regulating the expression of AKR1C3 through the TLR2 pathway. In vitro and in vivo experiments demonstrated that GATA6 knockdown reduced ferroptosis, improved cell viability, and mitigated extracellular matrix degradation, whereas GATA6 overexpression exacerbated these processes. Furthermore, AKR1C3 was found to be crucial for GATA6-mediated ferroptosis, and modulation of the TLR2-AKR1C3 axis significantly impacted the degeneration of NPCs. These findings suggest that targeting GATA6 and its downstream TLR2-AKR1C3 pathway may provide new therapeutic approaches for IVDD.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1174-1186"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of mRNA Modifications in Bone Diseases.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104460

Zehui Li, Keyu Meng, Shanwei Lan, Zhengda Ren, Zhongming Lai, Xiang Ao, Zhongyuan Liu, Jiajia Xu, Xiaoyi Mo, Zhongmin Zhang

{"title":"The Role of mRNA Modifications in Bone Diseases.","authors":"Zehui Li, Keyu Meng, Shanwei Lan, Zhengda Ren, Zhongming Lai, Xiang Ao, Zhongyuan Liu, Jiajia Xu, Xiaoyi Mo, Zhongmin Zhang","doi":"10.7150/ijbs.104460","DOIUrl":"10.7150/ijbs.104460","url":null,"abstract":"As a type of epigenetic modifications, mRNA modifications regulate the metabolism of mRNAs, thereby influencing gene expression. Previous studies have indicated that dysregulation of mRNA modifications is closely associated with the occurrence and progression of bone diseases (BDs). In this study, we first introduced the dynamic regulatory processes of five major mRNA modifications and their effects on the nucleus export, stability, and translation of mRNAs. We then summarized the mechanisms of mRNA modifications involved in the development of osteoporosis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, fractures, osteomyelitis, and osteosarcoma. Finally, we reviewed therapeutic strategies for BDs based on the above mechanisms, focusing on regulating osteoblast and osteoclast differentiation, inhibiting cellular senescence and injury, and alleviating inflammation. This review identified mRNA modifications as potential targets for treating BDs and proposes perspectives on the diversity, targetability, and safety of mRNA-modifying therapies.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1065-1080"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105513

Haina Zhang, Wenqian Zhou, Xiang Wang, Hongbo Men, Jiqun Wang, Jianxiang Xu, Shanshan Zhou, Quan Liu, Lu Cai

{"title":"Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling.","authors":"Haina Zhang, Wenqian Zhou, Xiang Wang, Hongbo Men, Jiqun Wang, Jianxiang Xu, Shanshan Zhou, Quan Liu, Lu Cai","doi":"10.7150/ijbs.105513","DOIUrl":"10.7150/ijbs.105513","url":null,"abstract":"Obesity increases the risk of metabolic syndrome including insulin resistance, dyslipidemia, and cardiovascular disease. We demonstrated insulin resistance, cardiac hypertrophy, and cardiac inflammation in an obese mouse model induced by a high-fat diet (HFD). Caspase recruitment domain-containing protein 9 (CARD9) and B-cell lymphoma/leukemia 10 (BCL10) were upregulated, and p38 MAPK was activated in these mice. Zinc supplementation prevented these changes with upregulation of metallothionein (MT). Deletion of MT exacerbated palmitate-triggered expression of BCL10 and p38 MAPK activation and eliminated the protective benefits of zinc in palmitate-treated cardiomyocytes. Here we further investigated the mechanisms by which endogenous MT expression affects HFD-induced cardiac remodeling and the CARD9/BCL10/p38 MAPK pathway. Male MT knockout and 129S wild-type mice were assigned to receive either a normal diet or a HFD from 8-week-age for 18 weeks. MT knockout (KO) aggravated HFD-induced obesity and systemic metabolic disorder, reflected by increased body weight, perirenal white adipose tissue, and plasma cholesterol, and cardiac hypertrophy and fibrosis. Obese MT-KO mice had abundant cardiac macrophages, upregulated cardiac proinflammatory cytokines, chemokines, adhesion molecules, CARD9, and BCL10 and activated NF-κB. MT-KO exacerbated HFD-induced trace metal dyshomeostasis and oxidative stress. MT-KO combined with HFD-induced obesity synergistically promotes cardiac remodeling, possibly via trace metal dyshomeostasis-induced oxidative stress to trigger CARD9/BCL10-mediated NF-κB activation.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1032-1046"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of nitric oxide generation and consumption.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105016

Husam M Abu-Soud, Olivia G Camp, Jayanth Ramadoss, Charalampos Chatzicharalampous, George Kofinas, Jason D Kofinas

{"title":"Regulation of nitric oxide generation and consumption.","authors":"Husam M Abu-Soud, Olivia G Camp, Jayanth Ramadoss, Charalampos Chatzicharalampous, George Kofinas, Jason D Kofinas","doi":"10.7150/ijbs.105016","DOIUrl":"10.7150/ijbs.105016","url":null,"abstract":"Nitric oxide (NO), originally discovered for its role in cardiovascular function, is a key molecule in physiological processes including metabolism, neurotransmission (including memory, learning, neuroprotection and synaptic plasticity), immunity, reproduction, and much more. NO can be synthesized by the catalytic activity of the enzyme nitric oxide synthase (NOS), which is found biologically in three isoforms, or nonenzymatically based on simple reduction of nitrate and nitrite or by the NO-donor S-nitrosothiol (R-SNO). Importantly, the deficiency of NO has been noted in a wide range of pathologies including cardiovascular disease, cancer, erectile dysfunction, male and female infertility, and mitochondrial disease. While there are several pathways that can lead to a reduction in the bioavailability of NO (i.e., consumption, inhibition, and substrate competition) it is the conclusion of the authors that multiple pathways co-exist in pathological states. This article outlines for the first time the major pathways of NO generation, the importance of NO in health, NO scavenging and enzyme inhibition, and the potential benefits of supplementation.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1097-1109"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TTC7B triggers the PI4KA-AKT1-RXRA-FTO axis and inhibits colon cancer cell proliferation by increasing RNA methylation.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.102431

Qianwen Ren, Meiyi Xiang, Juanli Qiao, Zhaojun Liu, Ge Zhang, Liankun Gu, Jing Zhou, Wei Tian, Dajun Deng

{"title":"TTC7B triggers the PI4KA-AKT1-RXRA-FTO axis and inhibits colon cancer cell proliferation by increasing RNA methylation.","authors":"Qianwen Ren, Meiyi Xiang, Juanli Qiao, Zhaojun Liu, Ge Zhang, Liankun Gu, Jing Zhou, Wei Tian, Dajun Deng","doi":"10.7150/ijbs.102431","DOIUrl":"10.7150/ijbs.102431","url":null,"abstract":"TTC7B is the PI4KA-binding protein. The upstream regulatory network associated with the expression of genes involved in RNA N6-adenine (m6A) methylation is not clear. Bioinformatics analysis revealed that the expression levels of TTC7B, PI4KA, and FTO are positively correlated with each other across human tissues. These genes are consistently downregulated in many cancers. We initially confirmed the correlation of the expression of these genes in colon cancer tissues from patients (n=105) and reported that TTC7B downregulation was significantly associated with poor prognosis. We subsequently performed a series of biological experiments and demonstrated that TTC7B upregulated RXRA expression probably through the PI4KA-mediated AKT1 pathway and that RXRA was a transcription factor for the FTO gene. TTC7B inhibited the proliferation of colon cancer cells by increasing the recruitment of RXRA to the FTO promoter, increasing FTO expression, and decreasing the total RNA m6A level. Ablation of FTO demethylase activity completely abolished the inhibitory effect of TTC7B on the proliferation of cancer cells in vitro and in vivo. In conclusion, our study demonstrated for the first time that TTC7B triggers the RXRA-FTO axis through PI4KA binding, which leads to a decrease in total RNA m6A modification and the inhibition of colon cancer progression.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1127-1143"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein phosphatase EYA1 regulates the dephosphorylation and turnover of BCL2L12 to promote glioma development.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.99619

Tianzi Wei, Risheng Lin, Yi Lu, Dong-Yan Jin, Jian Zhang, Mai Har Sham

{"title":"Protein phosphatase EYA1 regulates the dephosphorylation and turnover of BCL2L12 to promote glioma development.","authors":"Tianzi Wei, Risheng Lin, Yi Lu, Dong-Yan Jin, Jian Zhang, Mai Har Sham","doi":"10.7150/ijbs.99619","DOIUrl":"10.7150/ijbs.99619","url":null,"abstract":"Glioma is the most prevalent and deadly type of intracranial tumor. Understanding the molecular drivers and their underlying mechanisms in glioma development is urgently needed. EYA1 is a unique protein phosphatase that drives gliomagenesis, yet its substrates remain largely uncharacterized. In this study, we identify BCL2L12 (BCL2-like 12), a critical oncoprotein in glioma, as a novel substrate of EYA1 phosphatase in glioma cells. Our findings demonstrate that EYA1 dephosphorylates BCL2L12 at threonine-33 (T33), which in turn protects BCL2L12 from ubiquitination and subsequent proteasomal degradation. Our results indicate that BCL2L12 partially mediates the oncogenic roles of EYA1 in promoting glioma cell proliferation, highlighting the significance of EYA1's dephosphorylation of BCL2L12 in tumor progression. Moreover, we validate a positive correlation between EYA1 and BCL2L12 protein levels in glioma patient samples. In summary, our study reveals how EYA1-BCL2L12 interaction functions in glioma development, implicating EYA1 as a potential therapeutic target for glioma treatment.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1081-1096"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USP5 Binds and Stabilizes EphA2 to Increase Nasopharyngeal Carcinoma Radioresistance.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-06 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.102461

Jie-Yu Tang, Yun-Xi Peng, Wei Zhu, Jie-Ya Qiu, Wei Huang, Hong Yi, Shan-Shan Lu, Juan Feng, Zheng-Zheng Yu, Di Wu, Qi Wen, Li Yuan, Jinwu Peng, Zhi-Qiang Xiao

{"title":"USP5 Binds and Stabilizes EphA2 to Increase Nasopharyngeal Carcinoma Radioresistance.","authors":"Jie-Yu Tang, Yun-Xi Peng, Wei Zhu, Jie-Ya Qiu, Wei Huang, Hong Yi, Shan-Shan Lu, Juan Feng, Zheng-Zheng Yu, Di Wu, Qi Wen, Li Yuan, Jinwu Peng, Zhi-Qiang Xiao","doi":"10.7150/ijbs.102461","DOIUrl":"10.7150/ijbs.102461","url":null,"abstract":"Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. However, the underlying mechanism of NPC radioresistance remains poorly understood, and the promising radiosensitizer for NPC radiotherapy is also lacked. Overexpression of USP5 and EphA2 has been linked to various cancers, and both the proteins have attracted considerable attention for the development of new anti-cancer drugs. Here, we report that USP5 interacts with EphA2, and increases EphA2 protein stability and expression by ubiquitin proteasome pathway in the NPC cells. Mebendazole (MBZ), a broad-spectrum anthelmintic drug, transcriptionally inhibits USP5 expression, and then promotes EphA2 ubiquitination degradation in the NPC cells. Functionally, USP5 enhances in vitro and in vivo NPC cell radioresistance via stabilizing EphA2, and MBZ decreases in vitro and in vivo NPC cell radioresistance via targeting USP5/EphA2 axis. Moreover, the levels of USP5 and EphA2 are significantly higher in the radioresistant NPCs than those in the radiosensitive NPCs, and both proteins for predicting patient prognosis are superior to individual protein. These findings suggest that USP5 binds and stabilizes EphA2 by ubiquitin proteasome pathway to promote NPC radioresistance, and MBZ increases NPC radiosensitivity by targeting USP5/EphA2 axis, and is a potential radiosensitizer in NPC and perhaps in other cancers.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"893-909"},"PeriodicalIF":8.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-06 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.100948

Xin Yu, Wei Pei, Bei Li, Shengrong Sun, Wenge Li, Qi Wu

{"title":"Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.","authors":"Xin Yu, Wei Pei, Bei Li, Shengrong Sun, Wenge Li, Qi Wu","doi":"10.7150/ijbs.100948","DOIUrl":"10.7150/ijbs.100948","url":null,"abstract":"Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer development. We further delineate the effects of exercise on immune cell function, demonstrating its potential to mitigate immunosenescence and enhance antitumor responses. We also discuss the implications of immunosenescence for the efficacy of immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapy, and explore the potential benefits of combining exercise with these interventions. Collectively, this review underscores the importance of understanding the complex relationship between immunosenescence, physical exercise, and antitumor immunity, paving the way for the development of innovative strategies to improve cancer outcomes in the aging population.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"910-939"},"PeriodicalIF":8.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0