Acta biochimica et biophysica Sinica最新文献

{"title":"RP11-439C15.4 inhibits the malignant progression of hepatocellular carcinoma via binding to DHX9 and facilitating its degradation.","authors":"Xuejiao Li, Zhongying Hu, Yina Sun, Tingting Wang, Xijing Yan, Qiang You, Kunhua Hu, Jia Yao, Xiaofeng Yuan, Rong Li","doi":"10.3724/abbs.2025122","DOIUrl":"https://doi.org/10.3724/abbs.2025122","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of hepatocellular carcinoma (HCC), but the functions and molecular mechanisms of large lncRNAs remain unclear. In this study, HCC data from The Cancer Genome Atlas (TCGA) and 116 HCC cases from our clinical center are used to identify a novel lncRNA, RP11-439C15.4, which is significantly downregulated in HCC. This downregulation is associated with poor prognosis in HCC patients. A series of <i>in vitro</i> and <i>in vivo</i> experiments demonstrate that RP11-439C15.4 significantly inhibits the proliferation, invasion, migration and sorafenib resistance of HCC cells. Further mechanistic investigations reveal that RP11-439C15.4 interacts with DExH-Box Helicase 9 (DHX9) to increase its ubiquitination and accelerate the degradation of DHX9, ultimately suppressing HCC progression. Modulation of DHX9 significantly reverses the effects of RP11-439C15.4 in HCC. In conclusion, this study identifies RP11-439C15.4 as a tumor suppressor and elucidates the regulatory mechanism of the RP11-439C15.4/DHX9 axis in HCC, providing valuable insights into the mechanisms of HCC progression and potential therapeutic targets.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658062","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":"Unique gene patterns lead to distinct functional phenotypes and chemosensitivity profiles among subclones obtained from a single glioblastoma cell line.","authors":"Daxing Xu, Yingdi Jiang, Jie Li, Lingli Gong, Zhenkun Yang, Bo Zhang, Koukou Li, Jian Zou","doi":"10.3724/abbs.2025091","DOIUrl":"https://doi.org/10.3724/abbs.2025091","url":null,"abstract":"<p><p>One of the characteristics of malignant tumors is heterogeneity, which refers to the molecular or genetic differences among progeny cells during tumor growth. This heterogeneity contributes to variations in the tumor growth rate, invasive ability, drug sensitivity, and prognosis. To gain a deeper understanding of the molecular background underlying tumor heterogeneity, we construct monoclonal cell lines derived from the glioblastoma (GBM) cell line U87-MG by limiting dilution assays. The selected CF5 and G11 subclones exhibit completely different cell morphologies and, more importantly, distinct functional phenotypes. CF5 exhibits stronger proliferative properties and chemoresistance, whereas G11 shows greater motility and invasion. Transcriptomic sequencing reveals great differences in gene expression among the CF5, G11, and U87 cell lines, and downregulated genes in individual clones are significantly enriched in gene sets related to extracellular matrix function. ITGA11 and ITGA6, as research subjects, are demonstrated to exclusively regulate functional phenotypes and chemotherapy sensitivity in CF5 or G11 cells. In U87 cells, combined knockdown of these two genes significantly inhibits tumor growth and increases chemotherapy sensitivity, but knockdown of either gene alone does not. In summary, these data reveal that even under uniform growth conditions, the heterogeneity of tumor cells and their diverse genetic backgrounds remain significant and persistent. This finding is crucial for accurately identifying tumor-related genes and their functional phenotypes, and a thorough understanding of the genetic and molecular background underlying tumor heterogeneity is essential for comprehensive cancer treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658063","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":"Substrate topography-induced osteogenesis of bone marrow stem cells by reducing the chromatin accessibility of YBX1.","authors":"Yan Lv, Weishu Dai, Huijing Zhang, Sirui Liu, Mengdie Liu, Xueyan Zhang, Luling Li, Ying Hu, Yi Liu, Lin Song","doi":"10.3724/abbs.2025065","DOIUrl":"https://doi.org/10.3724/abbs.2025065","url":null,"abstract":"<p><p>Stem cell fate is profoundly influenced by a complex interplay of biochemical and biophysical cues, with the latter increasingly recognized for its roles in cellular processes, yet the mechanisms are unclear. Since chromatin accessibility is a critical determinant in the processes of osteogenesis and bone repair, investigating the contributions of open chromatin regions (OCRs) to the intracellular signaling pathways triggered by topographical cues, which lead to osteogenic differentiation is highly valuable. This study explores the impact of the nanotopography of biomaterials on the osteogenic differentiation of human bone marrow stem cells (hBMSCs). By utilizing electrospun poly-L-lactide (PLLA) membranes with random fiber arrangements, we mimic the natural extracellular matrix (ECM) topography to study its effects on hBMSCs, contrasting them with flat PLLA controls. Through high-throughput Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq), we reveal that the nanotopography of electrospun surfaces promotes osteogenic differentiation by modulating the chromatin accessibility of the <i>YBX1</i> gene promoter, leading to its upregulation. Lentiviral knockdown experiments further confirm the crucial role of YBX1, revealing a reversal of the osteogenic effects induced by nanotopography. This study emphasizes the importance of YBX1 in the osteogenic response to the surface topography of biomaterials and suggests that nanotopographical cues could be harnessed to direct stem cell fate. These findings are important for developing biomaterials that promote specific stem cell outcomes in regenerative medicine. Our results further contribute to a deeper understanding of the mechanisms underlying stem cell differentiation in response to environmental cues and pave the way for the rational design of biomaterials with enhanced osteogenic potential. By elucidating the role of chromatin accessibility and specific transcription factors such as YBX1, this study highlights the intricate interplay between cell-material interactions and the intracellular signaling pathways that govern stem cell fate.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590220","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":"Modulation of Aβ ₄₂-induced toxic effects on the cultured neuronal network activity by extracellular matrix stiffness.","authors":"Zhongliang Wei, Hucheng Zhao, Chandramohan Muruganandham, Chongdong Jian","doi":"10.3724/abbs.2025095","DOIUrl":"https://doi.org/10.3724/abbs.2025095","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599079","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":"Integration of the hammerhead ribozyme into structured RNAs to measure ligand-binding events for riboswitch candidates and aptamers.","authors":"Shenglan Zhang, Yinghong Lin, Ting Gao, Binfen Chen, Weibin Wu, Shanshan Fang, Kexin Fan, Yuqing Lai, Yezi Lin, Rongqin Ke, Sanshu Li","doi":"10.3724/abbs.2025097","DOIUrl":"https://doi.org/10.3724/abbs.2025097","url":null,"abstract":"<p><p>Some structured RNAs, such as riboswitches and aptamers, can bind to their cognate ligands and have been used in biosensors and gene expression control elements. However, current methods for detecting ligand binding to structured RNAs are either severely limited or inconvenient. In this study, we design a multibase pair bridge to integrate a hammerhead ribozyme into structured RNAs to detect ligand binding events. The experimental results demonstrate that the length of the bridge has a significant effect on the cleavage of the ribozyme; optimal cleavage can be achieved with three to six base pairs in the bridge. The dissociation constant ( <i>K</i> _D) values obtained through this method are in agreement with those determined by in-line probing techniques, and 1 pmol of allosteric ribozyme RNA is sufficient for measurement. We apply this method to evaluate the binding affinity of the riboswitch candidate Motif_9307. Our findings indicate that this motif has no binding affinity for S-adenosylmethionine or several other tested ligands, which is consistent with the results of the in-line probing experiments. Notably, our method reveals an increase in cleavage activity when yeast extract is added as a mixture of ligands, suggesting that the ligand of Motif_9307 is present in the extract. In conclusion, we develop an alternative approach for measuring ligand binding events associated with riboswitch candidates and aptamers.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599078","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":"Exploring the antitumor effect of curcumin-piperlongumine hybrid molecule (CP) on EGFR-TKI-resistant non-small cell lung cancer using network pharmacological analysis and experimental verification.","authors":"Shiyu Wang, Yinshuang Lai, Huijing Huang, Jing Yuan, Shanxin Li, Min Hui, Peipei Wang, Bingbing Chen, Zhiguo Liu, Jianchang Qian, Qianwen Zhang","doi":"10.3724/abbs.2025076","DOIUrl":"https://doi.org/10.3724/abbs.2025076","url":null,"abstract":"<p><p>EGFR-tyrosine kinase inhibitor (TKI) therapy is the most effective targeted therapy for non-small cell lung cancer (NSCLC). However, drug resistance remains a significant factor in the failure of lung cancer therapy. In the present study, we utilize network pharmacology, molecular docking, <i>in vitro</i> and <i>in vivo</i> experiments to explore the targets and biological mechanisms of CP, a novel curcumin-piperlongumine hybrid molecule, in EGFR-TKI-resistant NSCLC cells. The results reveal that CP exhibits enhanced biological activity compared to its parent compounds. CP can effectively inhibit cell proliferation by arresting cell cycle in the G2/M phase and inducing apoptosis. Mechanistically, CP-induced apoptosis is partially mediated by PI3K/AKT signaling pathway. These findings highlight the potential of CP as a promising therapeutic agent for EGFR-TKI-resistant lung cancer therapy.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599077","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":"KARs negatively regulate the immune response in lamprey.","authors":"Ruyu Zhuang, Zihao Yan, Shuyuan Zhang, Meixuan Li, Feng Sun, Ya Pang, Ding Li, Liang Zhao, Yinglun Han","doi":"10.3724/abbs.2025094","DOIUrl":"https://doi.org/10.3724/abbs.2025094","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574671","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":"Energy stress and adaptation strategy of tumor cells in different microenvironments: from primary tumors to distant metastases.","authors":"Mingzhe Xu, Junjie Fei, Zhi-Xiong Xiao, Yong Yi","doi":"10.3724/abbs.2025106","DOIUrl":"https://doi.org/10.3724/abbs.2025106","url":null,"abstract":"<p><p>Since the Warburg effect was first described in the 1920s, tumor energy metabolism has been a central focus of cancer research, emerging as a potential therapeutic target. The tumor microenvironment-including blood vessels, immune cells, stromal components, and other cell types-profoundly influences tumor cell metabolism. Variations in energy supply, oxygen availability, nutrient composition, and the accumulation of metabolic waste across different microenvironments challenge tumor cell survival and progression. In response, tumor cells adapt through flexible regulation and reprogramming of metabolic pathways. Although recent studies have explored metabolic adaptation mechanisms in various tumor microenvironments, the full spectrum from primary tumors to distant metastases remains unexplored. This review summarizes energy stress and adaptation maneuvers in tumor cells across different stages of tumor progression and offers a new perspective for comprehensive research to explore therapeutic strategies targeting tumor metabolism.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574670","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":"CDDO-imidazolide ameliorates sepsis-induced ARDS by enhancing mitophagy via the Nrf2 pathway to prohibit alveolar macrophage pyroptosis and HMGB1 release.","authors":"Yajing Liu, Pengcheng Ye, Cijun Tang, Meiru Jiang, Yiru Shen, Xiangrui Wang, Lei Hou, Yupeng Zhao","doi":"10.3724/abbs.2025092","DOIUrl":"https://doi.org/10.3724/abbs.2025092","url":null,"abstract":"<p><p>Accumulating evidence suggests that NLRP3-mediated alveolar macrophage (AM) pyroptosis and subsequent high mobility group box protein 1 (HMGB1) secretion play significant roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Nrf2 has been shown to be individually involved in regulating pyroptosis. In this study, we investigate the ability of CDDO-imidazolide, a potent Nrf2 activator, to regulate AM pyroptosis and HMGB1 secretion in sepsis-associated ARDS, along with its underlying mechanism. The <i>in vitro</i> alveolar macrophage (AM) pyroptosis model, established by stimulating J774A.1 cells with LPS and ATP, was treated with CDDO-imidazolide or utilized <i>Nrf2</i>-knockout cells. The mice are intraperitoneally administered with CDDO-imidazolide before the <i>in vivo</i> sepsis-associated ARDS model is constructed via caecal ligation perforation and the Nrf2 inhibitor, ML385. <i>In vitro</i> studies reveal that the use of 3-MA to prohibit PINK1/Parkin-dependent mitophagy aggravates NLRP3-mediated pyroptosis and HMGB1 release in J774A.1 cells via LPS and ATP exposure. CDDO-imidazolide also significantly prevents NLRP3-mediated pyroptosis and HMGB1 release to increase PINK1/Parkin-dependent mitophagy, but these effects are not detected in <i>Nrf2</i>-knockout macrophages. Most importantly, CDDO-imidazolide significantly alleviates NLRP3 inflammasome protein expression in the lung tissues of septic mice and HMGB1 protein levels in the serum and bronchoalveolar lavage fluid (BALF), which can be reversed by ML385. Taken together, our results demonstrate that CDDO-imidazolide prominently protects the lungs by promoting Nrf2 activation and enhancing PINK1/Parkin mitophagy to inhibit AM pyroptosis and HMGB1 release. These findings provide novel insights for therapeutic strategies for sepsis-associated ARDS.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537725","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":"ArfGAP2 deficiency ameliorates autoinflammation by regulating STING signaling and proton channel activity.","authors":"Min Zhang, Yufei Wang, Zhenwang Zhao, Xiaobo Hu","doi":"10.3724/abbs.2025107","DOIUrl":"https://doi.org/10.3724/abbs.2025107","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537724","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}