{"title":"KAT8 facilitates the proliferation of cancer cells through enhancing E7 function in HPV-associated cervical cancer.","authors":"Anli Xu, Xiaoming Yang, Junwei Zhao, Shujun Kong, Qing Tang, Xiangzhi Li, Hongmei Qu, Guoyun Wang","doi":"10.3724/abbs.2025022","DOIUrl":"https://doi.org/10.3724/abbs.2025022","url":null,"abstract":"<p><p>Persistent human papillomavirus (HPV) infection serves as the principal etiological factor in cervical cancer, with the oncoprotein E7, which is encoded by the virus, playing a key role in tumorigenesis. However, targeted therapeutic strategies against E7 remain underexplored. KAT8, a lysine acetyltransferase, significantly contributes to oncogenesis through the regulation of transcription. However, its involvement in cervical cancer remains inadequately characterized. This study employs HPV18-positive HeLa and HPV16-positive SiHa cell lines to investigate how KAT8 modulates E7 expression and function in cervical cancer cells. Upon <i>KAT8</i> knockdown, a marked reduction in cell viability is observed, alongside a decrease in E7 expression. This is associated with elevated level of retinoblastoma protein (pRb) and decreased E2F1 expression, indicating that KAT8 depletion inhibits E7 expression, resulting in E2F1 inactivation and cell cycle arrest. Furthermore, KAT8 directly binds to the promoter regions of the HPV18 LCR, enhancing the transcription of the HPV18 E7 gene. This study also demonstrates that KAT8 is essential for the acetylation of E7 and plays a critical role in facilitating the interaction between pRb/E2F1 and E7 in cervical cancer cells. In conclusion, these results highlight KAT8 as a key driver of cervical cancer progression, promoting the expression of HPV E7 and its associated oncogenic signaling pathways.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Divergent roles of PKM2 in regulating PD-L1 and PD-L2 expression and their implications in human and mouse cancer models.","authors":"Shuo He, Shujuan Luo, Bangwu Cai, Jiao Chen, Yao Zhang, Feng Zhao, Qing Liu, Tao Liu, Wei Wang, Tianyuan Peng, Xiaomei Lu, Shutao Zheng","doi":"10.3724/abbs.2025019","DOIUrl":"https://doi.org/10.3724/abbs.2025019","url":null,"abstract":"<p><p>Cancer cells evade immune detection through checkpoint molecules like PD-L1 and PD-L2 which suppress T-cell activation. While PD-L1 is well-studied, the role of PD-L2 remains unclear. Pyruvate kinase M2 (PKM2), a metabolic enzyme, influences immune checkpoint regulation, but its role in PD-L1 and PD-L2 modulation is not well defined. Here, we investigate the role of pyruvate kinase M2 (PKM2) in modulating the immune checkpoint molecules PD-L1 and PD-L2 via GATA3 in cancer cells, with insights from both human and mouse models. We find that PKM2 enhances PD-L1 expression while inhibiting PD-L2, a dual regulatory mechanism that facilitates immune evasion. Knockdown and overexpression experiments revealed GATA3 as a key mediator. <i>PKM2</i> knockout reduced GATA3 level, leading to decreased PD-L1 and increased PD-L2 expression. Chromatin immunoprecipitation (ChIP)-qPCR demonstrates that GATA3 functions as a direct transcription factor capable of binding to the promoters of <i>PD-L1</i> and <i>PD-L2</i>. <i>In silico</i> analyses of 81 esophageal squamous cell carcinoma (ESCC) cases from the TCGA database demonstrate that PKM2 mRNA is unrelated to PD-L1 and PD-L2 expression but is negatively correlated with CD8 <sup>+</sup> T-cell infiltration in ESCC. To further validate these findings, we establish a xenograft model using immune-competent C57/BL6N mice, where knockdown of <i>PKM2</i> results in significant downregulation of both PD-L1 and PD-L2 expression. Collectively, these findings underscore the divergent roles of PKM2 in regulating immune checkpoint expression in human and mouse cancer models and suggest that targeting the PKM2-GATA3 axis could enhance cancer immunotherapy by fine-tuning PD-L1 and PD-L2 levels.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pyruvate dehydrogenase alleviates macrophage autophagy in Hcy-induced ApoE <sup>-/-</sup> mice.","authors":"Qiujun Liu, Feng Li, Shutong Hu, Ning Ding, Fang Ma, Yinju Hao, Guizhong Li, Jiantuan Xiong, Huiping Zhang, Yideng Jiang","doi":"10.3724/abbs.2025021","DOIUrl":"https://doi.org/10.3724/abbs.2025021","url":null,"abstract":"<p><p>Macrophages play a protective role in atherosclerosis, whereas homocysteine (Hcy) is recognized as an independent risk factor for atherosclerosis. Defects in macrophage autophagy contribute to the formation of atherosclerotic plaques, and dysregulated energy metabolism is closely linked to the process of autophagy. However, the regulation of macrophage autophagy by pyruvate dehydrogenase (PDH), a key component of the PDH complex involved in energy and metabolic homeostasis, remains poorly understood in the context of atherosclerosis induced by Hcy. In our study, proteomic profiling identifies 748 upregulated proteins and 760 downregulated proteins in Hcy-treated macrophages. KEGG pathway analysis reveals significant enrichment of differentially expressed proteins in metabolism-related pathways, including those related to the biosynthesis of amino acids, carbon metabolism, and glycolysis/gluconeogenesis. Additionally, we explore the role of PDH in mediating Hcy-induced atherosclerosis in ApoE <sup>-/-</sup> mice. The results show a marked reduction in PDH expression and activity in Hcy-treated macrophages, leading to impaired autophagy. Notably, PDH activation enhances the assembly of the autophagy initiator ULK1-FIP200-Atg13 complex through the modulation of the AMPK/mTOR signaling pathway, suggesting a potential therapeutic target for Hcy-induced atherosclerosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.","authors":"Zuping Wu, Yuzhe Guan, Qian Chen, Ruifeng Song, Jing Xie, Xin Zhang, Yan Wang, Qianming Chen, Xiaoyan Chen","doi":"10.3724/abbs.2025020","DOIUrl":"https://doi.org/10.3724/abbs.2025020","url":null,"abstract":"<p><p>Bone metabolism in bone tissue is constantly maintained in a state of dynamic equilibrium. The mass of bone and joint tissues is determined by both bone formation and bone resorption. It is hypothesized that disrupted metabolic balance leads to osteoporosis, osteoarthritis, rheumatoid arthritis, and bone tumors. Such disruptions often manifest as either a reduction or abnormality in bone mass and are frequently accompanied by pathological changes such as inflammation, fractures, and pain. α-Ketoglutarate (α-KG) serves as a pivotal intermediate in various metabolic pathways in mammals, significantly contributing to cellular energy metabolism, amino acid metabolism, and other physiological processes. α-KG may be a therapeutic target for a variety of bone-related diseases, such as osteoporosis, osteoarthritis, and rheumatoid arthritis, because of its role in maintaining the metabolic balance of bone. After the application of α-KG, bone loss and inflammation in bone tissue are alleviated. This review focuses on the regulatory effects of α-KG on various cells in bone and joint tissues. Owing to the regulatory effect of α-KG on the balance of bone metabolism, the application of α-KG in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis, bone tumors, and other bone tissue diseases has been clarified.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to: Overexpression of PTEN induces cell growth arrest and apoptosis in human breast cancer ZR-75-1 cells.","authors":"Xiangyong Li, Guanping Lin, Binhua Wu, Xin Zhou, Keyuan Zhou","doi":"10.3724/abbs.2024244","DOIUrl":"https://doi.org/10.3724/abbs.2024244","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Liu, Jiemin Yin, Youqiang Meng, Congrui Ye, Junhui Chen, Sa Wang, Wen Yin, Po Gao, Yingfu Jiao, Weifeng Yu, Yinghui Fan
{"title":"Similarities and differences in the response and molecular characteristics of peripheral sensory neurons associated with pain and itch.","authors":"Li Liu, Jiemin Yin, Youqiang Meng, Congrui Ye, Junhui Chen, Sa Wang, Wen Yin, Po Gao, Yingfu Jiao, Weifeng Yu, Yinghui Fan","doi":"10.3724/abbs.2024202","DOIUrl":"https://doi.org/10.3724/abbs.2024202","url":null,"abstract":"<p><p>Dorsal root ganglion (DRG) neurons are responsible for the primary detection and transmission of peripheral noxious stimuli, mainly pain and itch. However, as two distinct noxious sensations, how DRG neurons respond differently to and code pain and itch is still an attractive topic. Here, we investigate the response and activation spectrum of DRG neurons under peripheral pain and itch stimuli using <i>in vivo</i> two-photon calcium imaging and find differences in the response intensity to pain and itch between multisensory neurons (both pain and itch) and single-sensory neurons (either pain or itch). In addition, single-cell RNA sequencing (scRNA-seq) is used to reveal the heterogeneity of distinct subpopulations on the basis of their expressions of pain- or itch-related marker genes and to determine the similarities and differences in their transcriptomic changes under chronic pain and itch. Our results show that primary sensory neurons with different sensory patterns respond differently to the same nociceptive stimuli. Additionally, distinct clusters of neurons exhibit unique transcriptomic changes in the development of chronic pain and itch, which may offer new insights for treating these conditions.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tissue extracellular vesicles suppress neonatal cardiac regeneration: a Pak2-Erk1/2-mediated macrophage paracrine signaling.","authors":"Yongwei Li, Laihai Zhang, Yating Wu, Lu Wei, Zhenchun Zhang, Hanling Mo, Zhongmin Liu, Xianyun Wang, Yunli Shen, Hongming Zhu","doi":"10.3724/abbs.2024193","DOIUrl":"https://doi.org/10.3724/abbs.2024193","url":null,"abstract":"<p><p>Myocardial infarction leads to cardiomyocyte loss, and the compromised proliferative capacity of cardiomyocytes after birth hinders the process of heart repair, ultimately culminating in heart failure. Extracellular vesicles (EVs), known as cell-secreted \"messengers\", play a pivotal role in tissue pathophysiology. Here, we report the novel finding that myocardial tissue-derived vesicles from mice on postnatal day 8 (P8-EVs) possess the potential to modulate cardiomyocyte proliferation. Notably, direct administration of EVs derived from day 1 or day 8 (P1/P8) myocardial tissue does not impact neonatal cardiomyocyte proliferation or myocardial repair in mice with myocardial infarction. However, by leveraging bioinformatics, high-throughput omics, and single-cell analyses, we unveil that P8-EVs are enriched with the key gene p21 activated kinase 2 (Pak2), a regulator of macrophage reparative function. Through single-cell sequencing of P8 myocardial tissue, we identify macrophages as the cell type with the highest Pak2 content, implying a close association between macrophages and P8-EV function. Intriguingly, further investigations reveal that P8-EVs significantly promote M1-like polarization, augment phagocytosis, and affect factor secretion in macrophages. Co-culture experiments demonstrate that P8-EV-treated macrophages strongly suppress neonatal cardiomyocyte proliferation, and this effect is effectively reversed by a Pak2 inhibitor. Additional pathway intervention experiments reveal that P8-EVs activate the downstream Erk1/2 signaling pathway of Pak2. Collectively, our findings indicate that P8-EVs regulate macrophage paracrine activities through the Pak2-Erk1/2 axis, thereby influencing cardiomyocyte proliferation. This finding reveals a potential underlying mechanism for the compromised proliferative capacity of cardiomyocytes in adult mice.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Macrophage pyroptosis in atherosclerosis: therapeutic potential.","authors":"Jianying Ma, Yixian Wang, Wenna Xu, Hanjing Wang, Zhengdong Wan, Jiawei Guo","doi":"10.3724/abbs.2025004","DOIUrl":"https://doi.org/10.3724/abbs.2025004","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipid-rich plaques in arterial walls, leading to cardiovascular events such as myocardial infarction and stroke. Macrophage pyroptosis, a form of programmed cell death driven by the NLRP3 inflammasome and caspase-1 activation, plays a critical role in the progression and destabilization of atherosclerotic plaques. This review explores the molecular mechanisms underlying macrophage pyroptosis and their significant contributions to AS pathogenesis. Recent advancements have highlighted the therapeutic potential of targeting key components of the pyroptotic pathway, including the use of nanotechnology to increase drug delivery specificity. These strategies are promising for reducing inflammation, stabilizing plaques, and mitigating the clinical impact of AS. Future studies should focus on translating these findings into clinical applications to develop effective treatments that can halt or reverse AS progression by modulating macrophage pyroptosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiwei Gu, Zhen Li, Xinyi Li, Ziyao Yang, Xi Xu, Yanjia Wang, Xiaohan Li, Kaiyue Qin, Guizhong Li, Li Xue, Xiaoling Yang
{"title":"MiR-133b-3p attenuates angiotensin II-induced cardiac hypertrophy through the inhibition of apoptosis by targeting <i>CDIP1</i>.","authors":"Jiwei Gu, Zhen Li, Xinyi Li, Ziyao Yang, Xi Xu, Yanjia Wang, Xiaohan Li, Kaiyue Qin, Guizhong Li, Li Xue, Xiaoling Yang","doi":"10.3724/abbs.2024181","DOIUrl":"https://doi.org/10.3724/abbs.2024181","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as essential regulators that play important roles in the development of multiple systems. Recent studies have identified significant roles for miRNAs in the progression of cardiac hypertrophy. This study aims to investigate the effects of miR-133b-3p on angiotensin II (Ang II)-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Our experimental results reveal that miR-133b-3p expression is significantly decreased in both animal and cell models of cardiac hypertrophy induced by Ang II. Overexpression of miR-133b-3p reverses the hypertrophic manifestations and apoptosis induced by Ang II. Through bioinformatics analysis and dual-luciferase reporter assays, <i>CDIP1</i> (cell death inducing p53 target 1) is identified as a direct target of miR-133b-3p, and the overexpression of miR-133b-3p reduces <i>CDIP1</i> expression. Additionally, <i>CDIP1</i> silencing suppresses cardiomyocyte hypertrophy and apoptosis induced by Ang II. In summary, these results suggest that miR-133b-3p may serve as a potential diagnostic marker for cardiac hypertrophy and that the upregulation of miR-133b-3p inhibits cardiac hypertrophy by targeting <i>CDIP1</i>.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huihui Ju, Yile Zhou, Wanting Wei, Yan Hu, Hongwei Fang, Zhouyi Chen, Xia Sun, Yi Shi, Hao Fang
{"title":"Ageing-associated gut dysbiosis deteriorates mouse cognition.","authors":"Huihui Ju, Yile Zhou, Wanting Wei, Yan Hu, Hongwei Fang, Zhouyi Chen, Xia Sun, Yi Shi, Hao Fang","doi":"10.3724/abbs.2024217","DOIUrl":"https://doi.org/10.3724/abbs.2024217","url":null,"abstract":"<p><p>Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide <i>in vitro</i>. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe <i>Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus</i> in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of <i>Lactobacillales</i>, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}