International Journal of Biochemistry & Cell Biology最新文献

Identification of a liver fibrosis and disease progression-related transcriptome signature in non-alcoholic fatty liver disease

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-03 DOI: 10.1016/j.biocel.2025.106751

Li-Xin Pan , Wei Tian , Zhi-Hao Huang , Jian-Rong Li , Jia-Yong Su , Qiu-Yan Wang , Xiao-Hui Fan , Jian-Hong Zhong

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. In vitro experiments were conducted to evaluate the expression levels of hub genes, and IL6 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 IL6 in HSC activation deserves more investigation in the context of NAFLD.

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引用次数: 0

Multi-omics analysis of transcriptome and proteome reveals that BAZ1A and BAZ2A have common and individual regulatory roles in hepatocellular carcinoma

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106730

Yan Liu , Fenglin Dong , Shuqing Wang , Jinghua Wu , Liming Zhou , Wei Fang

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.

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引用次数: 0

5'tiRNA-33-CysACA-1 promotes septic cardiomyopathy by targeting PGC-1α-mediated mitochondrial biogenesis 5'tiRNA-33-CysACA-1通过靶向pgc -1α介导的线粒体生物发生促进脓毒性心肌病。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106714

Ludong Yuan , Jing Li , Leijing Yin , Xiaofang Lin , Dan Ni , Chuanhuan Deng , Pengfei Liang , Bimei Jiang

Background

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.

Methods

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.

Results

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.

Conclusions

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.

背景：我们首次通过芯片分析发现感染性心肌病（SCM）中有158个trna来源的小rna （tsRNAs）表达改变，并选择上调最明显的5’tirna -33- cysaca -1作为代表，探讨tsRNAs在SCM中的作用和机制。方法：采用盲肠结扎穿刺法（CLP）建立小鼠脓毒症模型，采用实时荧光定量PCR （qRT-PCR）检测5’tirna -33- cysaca -1的表达。将LPS刺激巨噬细胞后产生的上清液作为条件培养基（CM）刺激H9C2，建立损伤细胞模型。CCK-8和LDH释放法检测细胞活力和细胞死亡。检测线粒体膜电位（MMP）、ATP生成、ROS生成和Mitotracker Red线粒体形态以评估线粒体功能。qRT-PCR验证了线粒体质量控制系统相关分子mRNA的表达。通过western blot、mRNA稳定性分析和救援实验检测5’tirna -33- cysaca -1调控过氧化物酶体增殖物激活受体γ -辅激活物-1α (PGC-1α)表达的机制。结果：5’tirna -33- cysaca -1在脓毒性心肌损伤心肌组织和H9C2细胞中表达升高。CM的刺激导致心肌细胞损伤和线粒体功能受损。在CM中转染5'tiRNA-33-CysACA-1 mimic进一步下调PGC-1α表达，抑制线粒体生物发生，从而损害线粒体功能，导致心肌细胞活性降低，细胞死亡增加。相比之下，转染抑制剂改善了上述生物过程。此外，mRNA稳定性分析和生物信息学分析表明，5'tiRNA-33-CysACA-1导致PGC-1α mRNA稳定性降低，从而下调PGC-1α的表达，促进SCM的发展。结论：5’tirna -33- cysaca -1在SCM中表达上调，通过靶向PGC-1α，降低PGC-1α mRNA的稳定性，抑制线粒体生物发生，导致线粒体功能障碍，促进SCM的发生。

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引用次数: 0

Corrigendum to “Dimerization of ZIP promotes its transcriptional repressive function and biological activity” [Int. J. Biochem. Cell Biol. 44 (2012) 886–895] “ZIP的二聚化促进其转录抑制功能和生物活性”的更正[Int.]学生物化学j。中国生物医学工程学报，2014(5):387 - 398。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106715

Bin Gui , Xiao Han , Yu Zhang , Jing Liang , Dandan Wang , Chenghao Xuan , Zhipeng Yu , Yongfeng Shang

引用次数: 0

Influence of the ERK/CHGB pathway in breast cancer progression under chronic stress 慢性应激下ERK/CHGB通路对乳腺癌进展的影响

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106733

Yue Wang , Xi Hou , Zijing Wu , Junyu Ren , Yanfang Zhao

Background

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.

Methods

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.

Results

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.

Conclusion

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.

背景：乳腺癌是女性最常见的恶性肿瘤之一，其发展涉及多种复杂的分子机制。已知细胞外信号调节激酶（ERK）和嗜铬颗粒蛋白B （CHGB）在多种癌症中起关键作用。本研究旨在探讨沙丁胺醇模拟慢性应激环境下ERK/CHGB通路对乳腺癌发生发展的影响。方法：采用雌性BALB/c小鼠建立乳腺癌模型，将其分为对照组、沙丁胺醇治疗组和沙丁胺醇抑制剂治疗组。采用细胞培养、免疫组织化学、Western Blot、实时荧光定量PCR和Transwell迁移实验来评估沙丁胺醇和ERK/CHGB通路的影响。结果：沙丁胺醇治疗可显著增强乳腺癌细胞的增殖、迁移和侵袭性，与ERK通路激活和CHGB表达增加有关。沙丁胺醇抑制剂治疗组对这些作用有明显的抑制作用。此外，ERK/CHGB通路在细胞外应激环境下的相互作用为乳腺癌细胞的存活和增殖提供了有利条件。结论：本研究表明沙丁胺醇模拟的慢性应激环境可通过ERK/CHGB通路促进乳腺癌细胞的恶性行为。这些发现为乳腺癌治疗提供了新的分子靶点，并强调了在癌症治疗中控制慢性应激和阻断特定分子途径的潜在重要性。

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引用次数: 0

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] “ROCK抑制通过Rac1驱动的ROS产生降低突变型p53胶质母细胞瘤对基因毒性应激的敏感性”的更正[j]。学生物化学j。生物化学学报[j].安徽农业大学学报，2016,34(2):1064 -1064。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106732

Yuli Thamires Magalhaes, Fabio Luis Forti

引用次数: 0

A testis-specific long non-coding RNA, 1700052I22Rik, regulates spermatid chromatin condensation in mice 睾丸特异性长非编码 RNA 1700052I22Rik 可调节小鼠精子染色质凝聚。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106725

Mengzhen Li , Zexuan Zhang , Qi Geng , Yan Lu , Shiying Miao , Xingguang Zhang , Wei Song , Kai Li

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.

长链非编码rna （lncRNAs）作为多种功能调节剂在睾丸中大量表达。然而，许多睾丸特异性或优先表达的lncrna仍未被表征。在这里，我们报道了睾丸特异性lncRNA 1700052I22Rik，它在精子发生过程中表现出动态表达模式。我们的研究结果表明，在小鼠中敲除1700052I22Rik会导致雄性精子数量减少和生育能力低下，以及精子染色质凝结缺陷。我们进一步阐明了1700052I22Rik通过与Y-box结合蛋白2 （YBX2）相互作用调节鱼精蛋白1 （PRM1）翻译的潜在机制。总之，我们的研究结果揭示了睾丸特异性lncRNA 1700052I22Rik在调节小鼠精细胞染色质凝聚中的关键作用，为lncRNA在精子发生中的功能和诊断和治疗男性不孕症的潜在靶点提供了新的见解。

引用次数: 0

GABPα targeted by miR-378a-5p inhibits the growth and angiogenesis of colorectal carcinoma miR-378a-5p靶向GABPα抑制结直肠癌的生长和血管生成。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2024.106729

Mengyi Wang , Jiangfa Qi , Zhenlin Tan , Runlong Zhou , Qing Zhuo , Xiaotong Deng , Zhenrong Wang , Ruijie Zhou , Fan Li , Yao Xu

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 in vivo 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.

考虑到结直肠癌的恶性程度高、复发率高、预后差，探索有前景的靶点是结直肠癌治疗的迫切策略。最近的研究表明，GABPα在癌症侵袭性中起作用，但其在结直肠癌进展中的确切功能和调节机制尚不清楚。本研究旨在探讨GABPα及其上游调节因子miR-378a-5p在调节癌症进展中的生物学作用。通过综合数据挖掘和qPCR分析GABPα和miR-378a-5p的表达水平。采用CCK-8法、创面愈合法、跨井侵入法、成管法和裸鼠异种移植模型评价GABPα的功能作用。我们还进行了共转染实验来研究miR-378a-5p和GABPα之间的调控关系。我们发现GABPα在人结直肠癌组织和细胞系中表达显著下调。功能实验显示，GABPα过表达可抑制结直肠癌细胞的增殖、迁移、侵袭和血管生成，体内实验进一步证实了GABPα的抑制作用。此外，miR-378a-5p在结直肠癌中表达上调，GABPα被确定为miR-378a-5p的直接靶点，荧光素酶报告基因检测证实了这一点。此外，GABPα的过表达部分抵消了miR-378a-5p诱导的癌细胞恶性行为的增强。我们的研究结果表明，miR-378a-5p通过直接靶向GABPα促进结直肠癌的侵袭性进展，突出了这一调节轴作为结直肠癌的潜在治疗靶点。

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引用次数: 0

Priming human bone marrow-derived mesenchymal stromal cells with signaling modifiers boosts their functionality: Potential application in regenerative therapies 用信号调节剂诱导人骨髓间充质间质细胞增强其功能：在再生治疗中的潜在应用。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2025.106734

Vaijayanti Kale

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 cost-effective and time-efficient 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 primed 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.

从骨髓、脐带、脐带血等组织中分离的间充质间质细胞（MSCs）常被用作体外扩增造血干细胞/祖细胞（hsc /HSPCs）的饲养层。它们也与造血干细胞共输注以提高移植疗效。然而，来自非造血组织的间充质干细胞可能具有次优的造血支持能力。同样，已知MSCs的功能在连续体外培养后会下降-这是一种不可避免的操作，以获得临床相关的细胞数量。因此，有必要增强长期培养的间充质干细胞的造血支持能力，以便在临床应用前用于造血干细胞。在这里，我展示了用适当选择的信号调节剂和整合素激活生物活性肽引发人骨髓源性间充质干细胞（BMSCs）增强其造血支持能力，从骨髓源性单核细胞（MNCs）形成的大量菌落以及CD34+ hsc的广泛增殖与它们短暂相互作用可见一斑。在骨髓间充质干细胞中注入信号调节剂是一种具有成本效益和时间效率的过程，因为合成这些小分子化合物相对便宜，这在临床环境中具有优势。在供体造血干细胞/造血干细胞与引物骨髓间充质干细胞输注到受体体内之前短暂相互作用的方法可以节省造血干细胞长期体外扩增的成本。在确定合适的药理学调节剂对靶细胞有预期的作用后，这一概念也可以在其他再生医学方案中找到应用。

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引用次数: 0

Bemcentinib enhances sensitivity to estrogen receptor inhibitors in breast cancer cells 贝美替尼增强乳腺癌细胞对雌激素受体抑制剂的敏感性

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.biocel.2025.106750

Gyeongmi Kim , Se Hee Ahn , Se-Kyeong Jang , Selim Kim , Hyunggee Kim , Ki Soo Park , Hyeon-Ok Jin , Chan Sub Park , Min-Ki Seong , Hyun-Ah Kim , In-Chul Park

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.

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引用次数: 0