International Journal of Biochemistry & Cell Biology最新文献

{"title":"Identification of a liver fibrosis and disease progression-related transcriptome signature in non-alcoholic fatty liver disease","authors":"Li-Xin Pan ,&nbsp;Wei Tian ,&nbsp;Zhi-Hao Huang ,&nbsp;Jian-Rong Li ,&nbsp;Jia-Yong Su ,&nbsp;Qiu-Yan Wang ,&nbsp;Xiao-Hui Fan ,&nbsp;Jian-Hong Zhong","doi":"10.1016/j.biocel.2025.106751","DOIUrl":"10.1016/j.biocel.2025.106751","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis is closely associated with long-term outcomes of patients. This study aimed to establish a transcriptome signature to distinguish NAFLD patients with mild or advanced fibrosis and to monitor disease progression. Using least absolute shrinkage selection operator regression, we identified a signature of 11 hub genes by performing differential gene expression analysis in six bulk transcriptome profiles in the Gene Expression Omnibus database from liver fibrosis patients with different etiologies. Patients with NAFLD were classified using the 11-hub gene signature. Integrated analysis of signaling pathway enrichment, gene set enrichment, nearest template prediction, infiltration by hepatic stellate cells (HSCs) and pseudotime trajectories was performed on three bulk and one single-cell transcriptomes from NAFLD patients. Molecular features were compared between high-risk and low-risk groups, and associations were explored between hub gene signature expression and activation of HSCs. It was found that the high-risk group was characterized by advanced fibrosis stage, elevated risk for hepatocellular carcinoma, more significant infiltration by activated HSCs, as well as enrichment in signaling pathways related to fibrogenesis and NAFLD progression. Moreover, the 11-hub gene signature at the single-cell transcriptome level correlated with HSCs activation. <em>In vitro</em> experiments were conducted to evaluate the expression levels of hub genes, and <em>IL6</em> was found to be up-regulated in activated LX-2 cells showing lipid accumulation. Our findings suggest that the 11-hub gene signature can help identify fibrosis stage in patients with NAFLD and detect disease progression. We also suggest that the role of <em>IL6</em> in HSC activation deserves more investigation in the context of NAFLD.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106751"},"PeriodicalIF":3.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of transcriptome and proteome reveals that BAZ1A and BAZ2A have common and individual regulatory roles in hepatocellular carcinoma","authors":"Yan Liu ,&nbsp;Fenglin Dong ,&nbsp;Shuqing Wang ,&nbsp;Jinghua Wu ,&nbsp;Liming Zhou ,&nbsp;Wei Fang","doi":"10.1016/j.biocel.2024.106730","DOIUrl":"10.1016/j.biocel.2024.106730","url":null,"abstract":"<div><div>This study employs an integrative multi-omics approach to elucidate the complex regulatory roles of BAZ1A and BAZ2A, subunits of the ISWI chromatin remodeling complexes, in hepatocellular carcinoma (HCC). Utilizing siRNA-mediated knockdown, combined with high-throughput RNA sequencing and mass spectrometry, the researchers reveal distinct and overlapping functions of BAZ1A and BAZ2A in both transcriptional and proteomic regulation. The findings indicate that BAZ1A is primarily involved in ribosomal biogenesis and nucleolar function, while BAZ2A exerts significant influence on cell cycle progression and DNA repair mechanisms. Through a comprehensive analysis of the transcriptome and proteome following gene knockdown, the study highlights the intricate interplay between these two subunits, which contributes to the pathogenesis of HCC. This integrated approach not only uncovers their differential impact on gene expression and protein abundance but also reveals their involvement in alternative splicing events. Additionally, potential downstream targets and associated signaling pathways are identified, providing valuable insights into the molecular mechanisms underlying HCC development. The distinct roles of BAZ1A and BAZ2A in various cellular processes, along with their differential effects on gene and protein regulation, position them as promising therapeutic targets. These results offer new perspectives for understanding the molecular basis of HCC and suggest potential avenues for targeted therapies.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106730"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5'tiRNA-33-CysACA-1 promotes septic cardiomyopathy by targeting PGC-1α-mediated mitochondrial biogenesis","authors":"Ludong Yuan ,&nbsp;Jing Li ,&nbsp;Leijing Yin ,&nbsp;Xiaofang Lin ,&nbsp;Dan Ni ,&nbsp;Chuanhuan Deng ,&nbsp;Pengfei Liang ,&nbsp;Bimei Jiang","doi":"10.1016/j.biocel.2024.106714","DOIUrl":"10.1016/j.biocel.2024.106714","url":null,"abstract":"<div><h3>Background</h3><div>We revealed for the first time that the expression of 158 tRNA-derived small RNAs (tsRNAs) was altered in septic cardiomyopathy (SCM) by microarray analysis, and we selected 5'tiRNA-33-CysACA-1, which was the most significantly up-regulated, as a representative to explore the roles and mechanisms of tsRNAs in SCM.</div></div><div><h3>Methods</h3><div>We constructed a sepsis model by cecum ligation and puncture (CLP) in mice and detected the expression of 5'tiRNA-33-CysACA-1 using quantitative real-time PCR (qRT-PCR). The supernatant generated after LPS stimulation of macrophages was used as the conditional medium (CM) to stimulate H9C2 and established the injured cell model. CCK-8 and LDH release assays were used to detect cell viability and cell death. Mitochondrial membrane potential (MMP), ATP production, ROS production, and Mitotracker Red mitochondrial morphology were assayed to assess mitochondrial function. Expression of mRNA for molecules related to the mitochondrial quality control system was verified by qRT-PCR. The mechanism by which 5'tiRNA-33-CysACA-1 regulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) expression was examined by western blot, mRNA stability analysis, and rescue experiments.</div></div><div><h3>Results</h3><div>Expression of 5'tiRNA-33-CysACA-1 was elevated in cardiac tissue and H9C2 cells during septic myocardial injury. Stimulation of the CM resulted in cardiomyocyte injury and impaired mitochondrial function. Transfection of 5'tiRNA-33-CysACA-1 mimic in CM further downregulated PGC-1α expression, inhibited mitochondrial biogenesis thereby impairing mitochondrial function and leading to decreased cardiomyocyte activity and increased cell death. In contrast, transfection of the inhibitor ameliorated the above biological processes. In addition, mRNA stability assay and bioinformatics analysis showed that 5'tiRNA-33-CysACA-1 led to a decrease in the stability of PGC-1α mRNA, which in turn downregulated the expression of PGC-1α and promoted the development of SCM.</div></div><div><h3>Conclusions</h3><div>5'tiRNA-33-CysACA-1 expression is upregulated in SCM and inhibits mitochondrial biogenesis by targeting PGC-1α and decreasing the stability of PGC-1α mRNA, leading to mitochondrial dysfunction and promoting the development of SCM.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106714"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 “Dimerization of ZIP promotes its transcriptional repressive function and biological activity” [Int. J. Biochem. Cell Biol. 44 (2012) 886–895]","authors":"Bin Gui ,&nbsp;Xiao Han ,&nbsp;Yu Zhang ,&nbsp;Jing Liang ,&nbsp;Dandan Wang ,&nbsp;Chenghao Xuan ,&nbsp;Zhipeng Yu ,&nbsp;Yongfeng Shang","doi":"10.1016/j.biocel.2024.106715","DOIUrl":"10.1016/j.biocel.2024.106715","url":null,"abstract":"","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106715"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the ERK/CHGB pathway in breast cancer progression under chronic stress","authors":"Yue Wang ,&nbsp;Xi Hou ,&nbsp;Zijing Wu ,&nbsp;Junyu Ren ,&nbsp;Yanfang Zhao","doi":"10.1016/j.biocel.2024.106733","DOIUrl":"10.1016/j.biocel.2024.106733","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is one of the most common malignancies among women, and its development involves a variety of complex molecular mechanisms. Extracellular signal-regulated kinase (ERK) and Chromogranin B (CHGB) are known to play key roles in various cancers. This study aims to explore the impact of the ERK/CHGB pathway in a chronic stress environment simulated by salbutamol on the development of breast cancer.</div></div><div><h3>Methods</h3><div>This study utilized female BALB/c mice to establish a breast cancer model, dividing them into control, salbutamol-treated, and salbutamol-inhibitor-treated groups. Cell culture, immunohistochemistry, Western Blot, real-time fluorescent quantitative PCR, and Transwell migration assays were employed to assess the effects of salbutamol and the ERK/CHGB pathway.</div></div><div><h3>Results</h3><div>Salbutamol treatment significantly enhanced the proliferation, migration, and invasiveness of breast cancer cells, associated with the activation of the ERK pathway and the inhibition of CHGB. The salbutamol-inhibitor-treated group exhibited a marked suppression of these effects. Additionally, the interaction of the ERK/CHGB pathway in an extracellular stress environment provided advantages for the survival and proliferation of breast cancer cells.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that a chronic stress environment simulated by salbutamol can promote malignant behaviors in breast cancer cells through the ERK/CHGB pathway. These findings offer new molecular targets for breast cancer treatment and highlight the potential importance of managing chronic stress and blocking specific molecular pathways in cancer therapy.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106733"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 “ROCK inhibition reduces the sensitivity of mutant p53 glioblastoma to genotoxic stress through a Rac1- driven ROS production” [Int. J. Biochem. Mol. Bio. 164 (2023) 106474–106484]","authors":"Yuli Thamires Magalhaes,&nbsp;Fabio Luis Forti","doi":"10.1016/j.biocel.2024.106732","DOIUrl":"10.1016/j.biocel.2024.106732","url":null,"abstract":"","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106732"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A testis-specific long non-coding RNA, 1700052I22Rik, regulates spermatid chromatin condensation in mice","authors":"Mengzhen Li ,&nbsp;Zexuan Zhang ,&nbsp;Qi Geng ,&nbsp;Yan Lu ,&nbsp;Shiying Miao ,&nbsp;Xingguang Zhang ,&nbsp;Wei Song ,&nbsp;Kai Li","doi":"10.1016/j.biocel.2024.106725","DOIUrl":"10.1016/j.biocel.2024.106725","url":null,"abstract":"<div><div>Long non-coding RNAs (lncRNAs), serving as diverse functional regulators, are abundantly expressed in the testis. However, many testis-specific or preferentially expressed lncRNAs remain uncharacterized. Here, we report a testis-specific lncRNA, 1700052I22Rik, which exhibits a dynamic expression pattern during spermatogenesis. Our findings demonstrate that knockout of 1700052I22Rik in mice leads to reduced sperm counts and subfertility in males, as well as defective spermatid chromatin condensation. We further elucidate the underlying mechanism by which 1700052I22Rik modulates the translation of protamine 1 (PRM1) through interaction with Y-box binding protein 2 (YBX2). Collectively, our results uncover a crucial role for the testis-specific lncRNA 1700052I22Rik in regulating spermatid chromatin condensation in mice, providing novel insights into the functions of lncRNAs in spermatogenesis and potential targets for the diagnosis and treatment of male infertility.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106725"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABPα targeted by miR-378a-5p inhibits the growth and angiogenesis of colorectal carcinoma","authors":"Mengyi Wang ,&nbsp;Jiangfa Qi ,&nbsp;Zhenlin Tan ,&nbsp;Runlong Zhou ,&nbsp;Qing Zhuo ,&nbsp;Xiaotong Deng ,&nbsp;Zhenrong Wang ,&nbsp;Ruijie Zhou ,&nbsp;Fan Li ,&nbsp;Yao Xu","doi":"10.1016/j.biocel.2024.106729","DOIUrl":"10.1016/j.biocel.2024.106729","url":null,"abstract":"<div><div>Considering the high degree of malignancy, recurrence rate and poor prognosis, exploring promising targets is an imperious strategy for colorectal carcinoma therapy. Recent studies have indicated that GABPα plays a role in cancer aggressiveness, but its exact function and regulatory mechanisms in colorectal cancer progression remain unclear. This study aims to explore the biological role of GABPα and its upstream regulator, miR-378a-5p, in modulating cancer progression. The expression levels of GABPα and miR-378a-5p were analyzed through comprehensive data mining and qPCR assays. The functional effects of GABPα were assessed using CCK-8, wound healing, transwell invasion assay, tube formation and xenograft model in nude mice. A co-transfection assay was also performed to investigate the regulatory relationship between miR-378a-5p and GABPα. We found that GABPα expression was significantly downregulated in human colorectal cancer tissues and cell lines. Functional assays revealed that GABPα overexpression suppressed the proliferation, migration, invasion and angiogenesis of colorectal cancer cells, and <em>in vivo</em> experiments further confirmed the inhibitory role of GABPα. Additionally, miR-378a-5p was upregulated in colorectal cancer, and GABPα was identified as a direct target of miR-378a-5p, as confirmed by luciferase reporter assays. Furthermore, overexpression of GABPα partially counteracted the enhanced malignant behaviors of cancer cells induced by miR-378a-5p. Our findings suggest that miR-378a-5p promotes the aggressive progression of colorectal cancer by directly targeting GABPα, highlighting this regulatory axis as a potential therapeutic target for colorectal carcinoma.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106729"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Priming human bone marrow-derived mesenchymal stromal cells with signaling modifiers boosts their functionality: Potential application in regenerative therapies","authors":"Vaijayanti Kale","doi":"10.1016/j.biocel.2025.106734","DOIUrl":"10.1016/j.biocel.2025.106734","url":null,"abstract":"<div><div>Mesenchymal stromal cells (MSCs) isolated from tissues such as bone marrow, cord, cord blood, etc., are frequently used as feeder layers to expand hematopoietic stem/ progenitor cells (HSCs/HSPCs) in vitro. They are also co-infused with the HSCs to improve the efficacy of transplantation. However, the MSCs sourced from non-hematopoietic tissues could have suboptimal hematopoiesis-supportive ability. Likewise, the functionality of the MSCs is known to decline after continuous in vitro culture – an unavoidable manipulation to get clinically relevant cell numbers. Hence, it may be necessary to boost the hematopoiesis-supportive ability of the long-term cultured MSCs so that they can, in turn, be used to prime the HSCs before their clinical applications. Here, I show that priming human bone marrow-derived MSCs (BMSCs) with appropriately selected signaling modifiers and integrin-activating bioactive peptides boosts their hematopoiesis-supportive ability, as seen by the formation of a significantly higher number of colonies from the bone marrow-derived mononuclear cells (MNCs) and extensive proliferation of CD34⁺ HSCS briefly interacted with them. Priming the BMSCs with signaling modifiers is a <em>cost-effective and time-efficient</em> process as synthesizing these small molecule compounds is relatively inexpensive – an advantage in clinical settings. The approach of briefly interacting the donor HSCs/HSPCs with the <em>primed</em> BMSCs just before their infusion into the recipients' bodies could save the cost of long-term ex vivo expansion of HSCs. This concept could also find applications in other regenerative medicine protocols after identifying suitable pharmacological modulators that have the desired effects on the target cells.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106734"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bemcentinib enhances sensitivity to estrogen receptor inhibitors in breast cancer cells","authors":"Gyeongmi Kim ,&nbsp;Se Hee Ahn ,&nbsp;Se-Kyeong Jang ,&nbsp;Selim Kim ,&nbsp;Hyunggee Kim ,&nbsp;Ki Soo Park ,&nbsp;Hyeon-Ok Jin ,&nbsp;Chan Sub Park ,&nbsp;Min-Ki Seong ,&nbsp;Hyun-Ah Kim ,&nbsp;In-Chul Park","doi":"10.1016/j.biocel.2025.106750","DOIUrl":"10.1016/j.biocel.2025.106750","url":null,"abstract":"<div><div>Estrogen receptor (ER)-positive breast cancer accounts for a substantial proportion of breast cancer cases and is typically managed using ER inhibitors, such as tamoxifen and fulvestrant. However, the development of resistance to these therapies is a significant clinical challenge, and the improvement of therapeutic strategies is crucial. This study aimed to investigate the potential of bemcentinib, a well-known AXL inhibitor, to enhance the sensitivity of MCF7 breast cancer cells to 4-hydroxytamoxifen (4-OHT) and fulvestrant. Our findings revealed that bemcentinib effectively decreased S6K1 phosphorylation and synergistically induced cell death when used in combination with ER inhibitors. Bemcentinib treatment also unexpectedly activated STAT3, and inhibition of STAT3 enhanced cell death induced by bemcentinib and 4-OHT. Notably, the combination of bemcentinib and 4-OHT effectively induced cell death even in tamoxifen-resistant MCF7 cells (MCF7-TR), highlighting its potential to overcome tamoxifen resistance. Interestingly, AXL knockdown did not enhance the sensitivity to 4-OHT or affect S6K1 signaling in either MCF7 or MCF7-TR cells, suggesting that the sensitizing effect of bemcentinib through S6K1 inhibition may be independent of AXL expression. Our findings suggest that bemcentinib treatment, particularly in combination therapy, could be a promising strategy for improving treatment efficacy and overcoming tamoxifen resistance in ER-positive breast cancer.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106750"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}