Cell Biology and Toxicology最新文献

{"title":"Deciphering the heterogeneity of neutrophil cells within circulation and the lung cancer microenvironment pre- and post-operation.","authors":"Fangming Liu, Xuanqi Liu, Yifei Liu, Dongsheng Chen, Xiaoxia Liu, Chuan Qin, Yuanlin Song, Hao Fang, Duojiao Wu","doi":"10.1007/s10565-024-09850-z","DOIUrl":"10.1007/s10565-024-09850-z","url":null,"abstract":"<p><p>Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils' automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"11"},"PeriodicalIF":6.1,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD36 inhibition reduces non-small-cell lung cancer development through AKT-mTOR pathway.","authors":"Hui Liu, Wentong Guo, Tianxiang Wang, Peichang Cao, Tingfeng Zou, Ying Peng, Tengteng Yan, Chenzhong Liao, Qingshan Li, Yajun Duan, Jihong Han, Baotong Zhang, Yuanli Chen, Dahai Zhao, Xiaoxiao Yang","doi":"10.1007/s10565-024-09848-7","DOIUrl":"10.1007/s10565-024-09848-7","url":null,"abstract":"<p><p>Lung cancer is the most common cause of cancer-related deaths worldwide and is caused by multiple factors, including high-fat diet (HFD). CD36, a fatty acid receptor, is closely associated with metabolism-related diseases, including cardiovascular disease and cancer. However, the role of CD36 in HFD-accelerated non-small-cell lung cancer (NSCLC) is unclear. In vivo, we fed C57BL/6J wild-type (WT) and CD36 knockout (CD36^-/-) mice normal chow or HFD in the presence or absence of pitavastatin 2 weeks before subcutaneous injection of LLC1 cells. In vitro, A549 and NCI-H520 cells were treated with free fatty acids (FFAs) to mimic HFD situation for exploration the underlying mechanisms. We found that HFD promoted LLC1 tumor growth in vivo and that FFAs increased cell proliferation and migration in A549 and NCI-H520 cells. The enhanced cell or tumor growth was inhibited by the lipid-lowering agent pitavastatin, which reduced lipid accumulation. More importantly, we found that plasma soluble CD36 (sCD36) levels were higher in NSCLC patients than those in healthy ones. Compared to that in WT mice, the proliferation of LLC1 cells in CD36^-/- mice was largely suppressed, which was further repressed by pitavastatin in HFD group. At the molecular level, we found that CD36 inhibition, either with pitavastatin or plasmid, reduced proliferation- and migration-related protein expression through the AKT/mTOR pathway. Taken together, we demonstrate that inhibition of CD36 expression by pitavastatin or other inhibitors may be a viable strategy for NSCLC treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"10"},"PeriodicalIF":6.1,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circFCHO2(hsa_circ_0002490) promotes the proliferation of melanoma by directly binding to DND1.","authors":"Yang Yang, Jianrui Li, Chuanyuan Wei, Lu Wang, Zixu Gao, Kangjie Shen, Yinlam Li, Ming Ren, Yu Zhu, Yiteng Ding, Chenlu Wei, Tianyi Zhang, Shaoluan Zheng, Nanhang Lu, Jianying Gu","doi":"10.1007/s10565-024-09851-y","DOIUrl":"10.1007/s10565-024-09851-y","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have been documented to play crucial roles in the biology of various cancers. However, their investigation in melanoma is still at an early stage, particularly as a broader mechanism beyond acting as miRNA sponges needs to be explored. We report here that circFCHO2(hsa_circ_0002490), a circRNA encompassing exons 19 and 20 of the FCHO2 gene, exhibited a consistent overexpression in melanoma tissues. Furthermore, elevated circFCHO2 levels demonstrated a positive correlation with the malignant phenotype and poor prognosis among the 158 melanoma patients studied. Besides, we observed that heightened levels of circFCHO2 promoted melanoma cell proliferation, migration, and invasion in vitro, along with contributing to tumor growth in vivo. Furthermore, we found differences in the secondary structure of circFCHO2 compared to most other circular RNA structures. It has fewer miRNA binding sites, while it has more RNA binding protein binding sites. We therefore speculate that circFCHO2 may have a function of interacting with RNA binding proteins. Mechanistically, it was confirmed by fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), and western blotting assays that circFCHO2 interacts with dead end protein homolog 1 (DND1) and reverses the inhibition of the PI3K/AKT signaling pathway by binding to DND1. Our findings reveal that circFCHO2 drives melanoma progression by regulating the PI3K/AKT signaling pathway through direct binding to DND1 and may serve as a potential diagnostic biomarker and therapeutic target for the treatment of melanoma.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"9"},"PeriodicalIF":6.1,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10838848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke","authors":"Wenjie Su, Xiang Yu, Shan Wang, Xu Wang, Zheng Dai, Yi Li","doi":"10.1007/s10565-024-09844-x","DOIUrl":"https://doi.org/10.1007/s10565-024-09844-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Stroke is a major medical problem, and novel therapeutic targets are urgently needed. This study investigates the protective role and potential mechanisms of the N6-methyladenosine (m6A) RNA methyltransferase METTL3 against cerebral injury resulting from insufficient cerebral blood flow.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this study, we constructed mouse MCAO models and HT-22 cell OGD/R models to mimic ischemic stroke-induced brain injury and neuronal damage. We generated NEDD4L knockout and METTL3 overexpression models and validated therapeutic effects using infarct volume, brain edema, and neurologic scoring. We performed qRT-PCR, western blotting, and co-immunoprecipitation to assess the influence of NEDD4L on ferroptosis markers and TFRC expression. We verified the effect of NEDD4L on TFRC ubiquitination by detecting half-life and ubiquitination. Finally, we validated the impact of METTL3 on NEDD4L mRNA stability and MCAO outcomes in both in vitro and in vivo experimental models.</p><h3 data-test=\"abstract-sub-heading\">Result</h3><p>We find NEDD4L expression is downregulated in MCAO models. Overexpressing METTL3 inhibits the iron carrier protein TFRC by upregulating the E3 ubiquitin ligase NEDD4L, thereby alleviating oxidative damage and ferroptosis to protect the brain from ischemic injury. Mechanistic studies show METTL3 can methylate and stabilize NEDD4L mRNA, enhancing NEDD4L expression. As a downstream effector, NEDD4L ubiquitinates and degrades TFRC, reducing iron accumulation and neuronal ferroptosis.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In summary, we uncover the METTL3-NEDD4L-TFRC axis is critical for inhibiting post-ischemic brain injury. Enhancing this pathway may serve as an effective strategy for stroke therapy. This study lays the theoretical foundation for developing m6A-related therapies against ischemic brain damage.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"27 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LOXL1 promotes tumor cell malignancy and restricts CD8 + T cell infiltration in colorectal cancer.","authors":"Chenxi Li, Siqi Chen, Xiaona Fang, Yaqing Du, Xin-Yuan Guan, Runhua Lin, Liang Xu, Ping Lan, Qian Yan","doi":"10.1007/s10565-024-09840-1","DOIUrl":"10.1007/s10565-024-09840-1","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a leading cause of cancer mortality globally. Lymph node metastasis and immunosuppression are main factors of poor prognosis in CRC patients. Lysyl oxidase like 1 (LOXL1), part of the lysyl oxidase (LOX) family, plays a yet unclear role in CRC. This study aimed to identify effective biomarkers predictive of prognosis and efficacy of immunotherapy in CRC patients, and to elucidate the prognostic value, clinical relevance, functional and molecular features, and immunotherapy predictive role of LOXL1 in CRC and pan-cancer.</p><p><strong>Methods: </strong>Weighted gene co-expression network analysis (WGCNA) was employed to explore gene modules related to tumor metastasis and CD8 + T cell infiltration. LOXL1 emerged as a hub gene through differential gene expression and survival analysis. The molecular signatures, functional roles, and immunological characteristics affected by LOXL1 were analyzed in multiple CRC cohorts, cell lines and clinical specimens. Additionally, LOXL1's potential as an immunotherapy response indicator was assessed, along with its role in pan-cancer.</p><p><strong>Results: </strong>Turquoise module in WGCNA analysis was identified as the hub module associated with lymph node metastasis and CD8 + T cell infiltration. Aberrant elevated LOXL1 expression was observed in CRC and correlated with poorer differentiation status and prognosis. Molecular and immunological characterization found that LOXL1 might mediate epithelial-mesenchymal transition (EMT) process and immunosuppressive phenotypes of CRC. Functional study found that LOXL1 enhanced tumor cell proliferation, migration and invasion. Moreover, high LOXL1 levels corresponded to reduced CD8 + T cell infiltration and predicted poor clinical outcomes of immunotherapy. Similar trends were also observed at the pan-cancer level.</p><p><strong>Conclusions: </strong>Our findings underscore the critical role of LOXL1 in modulating both malignancy and immunosuppression in CRC. This positions LOXL1 as a promising biomarker for predicting prognosis and the response to immunotherapy in CRC patients.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"6"},"PeriodicalIF":5.3,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFEB and TFE3 cooperate in regulating inorganic arsenic-induced autophagy-lysosome impairment and immuno-dysfunction in primary dendritic cells.","authors":"Guowei Xu, Huaguang Peng, Ran Yao, Yuqing Yang, Bing Li","doi":"10.1007/s10565-024-09841-0","DOIUrl":"10.1007/s10565-024-09841-0","url":null,"abstract":"<p><p>Arsenic (As) is a prevalent and hazardous environmental toxicant associated with cancer and various health problems, which has been shown suppressive effects on dendritic cells (DCs). Autophagy is essential for the innate and adaptive immune responses of DCs, and the transcription factors TFEB and TFE3 are key regulators of autophagic and lysosomal target genes. However, the detrimental alterations of the autophagy-lysosome pathway in As-exposed DCs and the possible coordinating roles of TFEB and TFE3 in the immune dysfunction of this cell are less understood. In this paper, we found that As exposure significantly impaired lysosomal number, lysosomal acidic environment, and lysosomal membrane permeabilization, which might lead to blocked autophagic flux in cultured DCs. Furthermore, our results confirmed that TFEB or TFE3 knockdown exacerbated the disorders of lysosome and the blockade of autophagic flux in As-exposed DCs, and also enhanced the inhibitory expression of co-stimulatory molecules Cd80 and Cd83; adhesion molecule Icam1; cytokines TNF-α, IL-1β, and IL-6; chemokine receptor Ccr7; and antigen-presenting molecules MHC II and MHC I. By contrast, overexpression of TFEB or TFE3 partially alleviated the above-mentioned impairment of DCs by inorganic As exposure. In conclusion, these findings reveal a previously unappreciated inhibition of lysosome-mediated degradation and damage of lysosomal membrane integrity leading to dysregulated autophagy and impaired immune functions of DCs by arsenicals, and also suggest TFEB and TFE3 as potential therapeutic targets for ameliorating As toxicity.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"4"},"PeriodicalIF":5.3,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m⁶A modification mediates SLC3A2/SLC7A5 translation in 3-methylcholanthrene-induced uroepithelial transformation.","authors":"Bixia Liu, Yifan Lv, Wenyu Hu, Yapeng Huang, Xiaoling Ying, Cong Chen, Haiqing Zhang, Weidong Ji","doi":"10.1007/s10565-024-09846-9","DOIUrl":"10.1007/s10565-024-09846-9","url":null,"abstract":"<p><p>3-Methylcholanthracene (3-MC) is one of the most carcinogenic polycyclic aromatic hydrocarbons (PAHs). Long-term exposure to PAHs has been thought of as an important factor in urothelial tumorigenesis. N⁶-methyladenosine (m⁶A) exists widely in eukaryotic organisms and regulates the expression level of specific genes by regulating mRNA stability, translation efficiency, and nuclear export efficiency. Currently, the potential molecular mechanisms that regulate m⁶A modification for 3-MC carcinogenesis remain unclear. Here, we profiled mRNA, m⁶A, translation and protein level using \"-omics\" methodologies, including transcriptomes, m⁶A profile, translatomes, and proteomics in 3-MC-transformed urothelial cells and control cells. The key molecules SLC3A2/SLC7A5 were screened and identified in 3-MC-induced uroepithelial transformation. Moreover, SLC7A5/SLC3A2 promoted uroepithelial cells malignant phenotype in vitro and in vivo. Mechanically, METTL3 and ALKBH5 mediated m⁶A modification of SLC3A2/SLC7A5 mRNA in 3-MC-induced uroepithelial transformation by upregulating the translation of SLC3A2/SLC7A5. Furthermore, programmable m⁶A modification of SLC3A2/SLC7A5 mRNA affected the expression of its proteins. Taken together, our results revealed that the m⁶A modification-mediated SLC3A2/SLC7A5 translation promoted 3-MC-induced uroepithelial transformation, suggesting that targeting m⁶A modification of SLC3A2/SLC7A5 may be a potential therapeutic strategy for bladder cancer related to PAHs.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"5"},"PeriodicalIF":6.1,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis.","authors":"Wensi Wu, Zhi Wang, Huiying Zhang, Xiaojun Zhang, Hui Tian","doi":"10.1007/s10565-024-09839-8","DOIUrl":"10.1007/s10565-024-09839-8","url":null,"abstract":"<p><p>Air pollution has greatly increased the risk of idiopathic pulmonary fibrosis (IPF). Circular RNAs (circRNAs) have been found to play a significant role in the advancement of IPF, but there is limited evidence of correlation between circRNAs and lung epithelial cells (LECs) in IPF. This research aimed to explore the influence of circRNAs on the regulation of EMT progression in LECs, with the objective of elucidating its mechanism and establishing its association with IPF. Our results suggested that the downregulation of circGRHPR in peripheral blood of clinical cases was associated with the diagnosis of IPF. Meanwhile, we found that circGRHPR was downregulated in transforming growth factor-beta1 (TGF-β1)-induced A549 and Beas-2b cells. It is a valid model to study the abnormal EMT progression of IPF-associated LECs in vitro. The overexpression of circGRHPR inhibited the abnormal EMT progression of TGF-β1-induced LECs. Furthermore, as the sponge of miR-665, circGRHPR released the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), thus promoting its downstream transforming growth factor beta receptor 2 (TGFBR2) ubiquitination. It is helpful to reduce the response of LECs to TGF-β1 signaling. In summary, circGRHPR/miR-665/NEDD4L axis inhibited the abnormal EMT progression of TGF-β1-induced LECs by promoting TGFBR2 ubiquitination, which provides new ideas and potential targets for the treatment of IPF.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"7"},"PeriodicalIF":5.3,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription to regulate SOCS2/SLC7A11 signaling in gastric cancer.","authors":"Jingyun Wang, Qiaoyu Jia, Shuqin Jiang, Wenquan Lu, Hanbing Ning","doi":"10.1007/s10565-024-09843-y","DOIUrl":"10.1007/s10565-024-09843-y","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the effect and mechanism of POU6F1 and lncRNA-CASC2 on ferroptosis of gastric cancer (GC) cells.</p><p><strong>Methods: </strong>GC cells treated with erastin and RSL3 were detected for ferroptosis, reactive oxygen species (ROS) level, and cell viability. The expression levels of POU6F1, lncRNA-CASC2, SOCS2, and ferroptosis-related molecules (GPX4 and SLC7A11) were also measured. The regulations among POU6F1, lncRNA-CASC2, FMR1, SOCS2, and SLC7A11 were determined. Subcutaneous tumor models were established, in which the expressions of Ki-67, SOCS2, and GPX4 were detected by immunohistochemistry.</p><p><strong>Results: </strong>GC patients with decreased expressions of POU6F1 and lncRNA-CASC2 had lower survival rate. Overexpression of POU6F1 or lncRNA-CASC2 decreased cell proliferation and GSH levels in GC cells, in addition to increasing total iron, Fe2+, MDA, and ROS levels. POU6F1 directly binds to the lncRNA-CASC2 promoter to promote its transcription. LncRNA-CASC2 can target FMR1 and increase SOCS2 mRNA stability to promote SLC7A11 ubiquitination degradation and activate ferroptosis signaling. Knockdown of SOCS2 inhibited the ferroptosis sensitivity of GC cells and reversed the effects of POU6F1 and lncRNA-CASC2 overexpression on ferroptosis in GC cells.</p><p><strong>Conclusion: </strong>Transcription factor POU6F1 binds directly to the lncRNA-CASC2 promoter to promote its expression, while upregulated lncRNA-CASC2 increases SOCS2 stability and expression by targeting FMR1, thereby inhibiting SLC7A11 signaling to promote ferroptosis in GC cells and inhibit GC progression.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"3"},"PeriodicalIF":5.3,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARRB1 downregulates acetaminophen-induced hepatoxicity through binding to p-eIF2α to inhibit ER stress signaling.","authors":"Yujun Luo, Yiming Lei, Haoxiong Zhou, Yan Chen, Huiling Liu, Jie Jiang, Chengfang Xu, Bin Wu","doi":"10.1007/s10565-024-09842-z","DOIUrl":"10.1007/s10565-024-09842-z","url":null,"abstract":"<p><p>Acetaminophen (APAP) stands as the predominant contributor to drug-induced liver injury (DILI), and limited options are available. β-Arrestin1 (ARRB1) is involved in numerous liver diseases. However, the role of ARRB1 in APAP-induced liver injury remained uncertain. Wild-type (WT) and ARRB1 knockout (KO) mice were injected with APAP and sacrificed at the indicated times. The histological changes, inflammation, endoplasmic reticulum (ER) stress, and apoptosis were then evaluated. Hepatic cell lines AML-12 and primary hepatocytes were used for in vitro analyses. Systemic ARRB1-KO mice were susceptible to APAP-induced hepatotoxicity, as indicated by larger areas of centrilobular necrosis area and higher levels of ALT, AST, and inflammation level. Moreover, ARRB1-KO mice exhibited increased ER stress (indicated by phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF2α)-activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein homologous protein (CHOP)) and apoptosis (indicated by cleaved caspase 3). Further rescue experiments demonstrated that the induction of apoptosis was partially mediated by ER stress. Overexpression of ARRB1 alleviated APAP-induced ER stress and apoptosis. Moreover, co-IP analysis revealed that ARRB1 directly bound to p-eIF2α and eIF2α. ARRB1 protected against APAP-induced hepatoxicity through targeting ER stress and apoptosis. ARRB1 is a prospective target for treating APAP-induced DILI.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"1"},"PeriodicalIF":6.1,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}