Biochimie最新文献_第6页

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IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-12-30 DOI: 10.1016/S0300-9084(25)00306-2

引用次数: 0

Premature aging in chronic kidney disease: Decoding senescence biomarkers and therapeutic opportunities 慢性肾脏疾病的过早衰老：解码衰老生物标志物和治疗机会。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-15 DOI: 10.1016/j.biochi.2025.10.008

Carlos Eduardo H.V. P.F. Braga , Jessyca S. de Brito , Marcia Ribeiro , Karen Salve Coutinho-Wolino , Bruna Regis , Bruna Calixto , Renata Cristina Bezerra Rodrigues , Angela Yee-Moon Wang , Peter Stenvinkel , Denise Mafra

Chronic kidney disease (CKD) is characterized by a premature aging phenotype. CKD-related stressors, such as inflammation, oxidative stress, the buildup of uremic toxins, hyperphosphatemia, mitochondrial dysfunction, sirtuin inhibition, and klotho deficiency, trigger cell cycle arrest, inducing senescence in tubular epithelial cells, endothelial cells, and podocytes, accelerating CKD progression and leading to the expression of senescence-related genes and the senescence-associated secretory phenotype (SASP). This condition promotes local (e.g., interstitial fibrosis, glomerulosclerosis, endothelial dysfunction) and systemic damage, including micro- and macrovascular dysfunction, early vascular aging, and an increased risk of cardiovascular mortality. Markers such as SA-β-gal, p16^INK4a, p21^CIP1, p53, and SASP components (e.g., IL-6, MCP-1, MMP-3), as well as telomere shortening and mitochondrial DNA accumulation, are frequently used to identify senescence. Despite their predictive potential, the application of these biomarkers for disease progression and cardiovascular complications remains underexplored in patients with CKD. This narrative review explores the complex relationship between senescence and CKD, reviews key senescence biomarkers, emphasizes their importance for diagnosis, and evaluates the potential of senotherapies to reduce complications of premature aging in this population.

慢性肾脏疾病（CKD）的特点是早衰表型。CKD相关的应激源，如炎症、氧化应激、尿毒症毒素的积累、高磷血症、线粒体功能障碍、sirtuin抑制和klotho缺乏，触发细胞周期阻滞，诱导小管上皮细胞、内皮细胞和足细胞衰老，加速CKD进展，导致衰老相关基因的表达和衰老相关分泌表型（SASP）。这种情况促进局部（如间质纤维化、肾小球硬化、内皮功能障碍）和全身损伤，包括微血管和大血管功能障碍、血管早期衰老和心血管死亡风险增加。诸如SA-β-gal、p16INK4a、p21CIP1、p53和SASP成分（如IL-6、MCP-1、MMP-3）以及端粒缩短和线粒体DNA积累等标记常被用于识别衰老。尽管具有预测潜力，但这些生物标志物在慢性肾病患者疾病进展和心血管并发症中的应用仍未得到充分探索。本文探讨了衰老与慢性肾病之间的复杂关系，综述了关键的衰老生物标志物，强调了它们在诊断中的重要性，并评估了衰老疗法在减少这一人群早衰并发症方面的潜力。

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引用次数: 0

The HEK293T cells manage overload by the overexpressed full-length Htt variants via proteasome activation HEK293T细胞通过蛋白酶体激活过表达全长Htt变异体来管理过载。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-21 DOI: 10.1016/j.biochi.2025.10.014

Nataliia N. Gotmanova , Tatiana V. Bobik , Viacheslav A. Kriachkov , Alexander A. Ezhov , Anna V. Bacheva

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a pathological mutation that results in the abnormal expansion of more than 37 consecutive trinucleotide repeats (CAG) in the HTT gene. These repeats encode the polyglutamine tract (polyQ tract) in the huntingtin protein (Htt). Progressive lethal Huntington's chorea is characterized by impaired motor activity and marked cerebral atrophy. The disease affects neurons in specific areas of the central nervous system, mainly GABAergic neurons in the striatum and cortex. It is believed that the neuron-specific proteotoxicity of mutant Htt (mHtt) results from its conformational instability and tendency to aggregate due to elongation of the polyQ-tract. However, recent structural findings challenge these assumptions. To elucidate some key aspects of the molecular mechanisms of HD, we describe the transient expression of full-length normal or mutant huntingtin in HEK293T eukaryotic cells, and options of isolation and purification of huntingtin variants according to the optimized procedure. The short-termed overexpression of Htt/mHtt has been demonstrated to be associated with elevated proteasome and non-proteasome caspase activity, and change in subunit expression. The cellular response to mHtt production manifested primarily as an increase in β1, β5i and in less extent β1i subunits as well as 11Sαβ expression, as observed through both Western blot and RT-qPCR. The microscopy study also revealed an enhancement in the β1i subunit content in HEK293T cells overexpressed Htt and especially mHtt suggesting an immunoproteasome activation.

亨廷顿氏病（HD）是一种常染色体显性神经退行性疾病，由病理突变引起HTT基因中超过37个连续三核苷酸重复（CAG）的异常扩增。这些重复序列编码亨廷顿蛋白（Htt）中的聚谷氨酰胺通道（polyQ通道）。进行性致死性亨廷顿舞蹈病的特征是运动活动受损和显著的脑萎缩。这种疾病影响中枢神经系统特定区域的神经元，主要是纹状体和皮层的gaba能神经元。据认为，突变体Htt （mHtt）的神经元特异性蛋白质毒性是由于其构象不稳定和多q通道伸长导致的聚集倾向。然而，最近的结构性发现挑战了这些假设。为了阐明HD的一些关键分子机制，我们描述了正常或突变的亨廷顿蛋白全长在HEK293T真核细胞中的瞬时表达，以及根据优化的程序分离和纯化亨廷顿蛋白变体的选择。Htt/mHtt的过表达已被证明与蛋白酶体和非蛋白酶体半胱天冬酶活性升高以及亚基表达的变化有关。通过Western blot和RT-qPCR观察到，细胞对mHtt产生的反应主要表现为β1、β5i和少量β1i亚基以及11Sαβ表达的增加。显微镜研究还发现，HEK293T细胞中β1i亚基含量增加，过量表达Htt，特别是mHtt，提示免疫蛋白酶体活化。

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引用次数: 0

Exploring the impact of prion protein N- and C-terminal fragments on the pathological transformation of alpha-synuclein 探讨朊蛋白N端和c端片段对α -突触核蛋白病理转化的影响。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-08 DOI: 10.1016/j.biochi.2025.10.004

Sofiya Kudryavtseva , Yulia Stroylova , Sviatlana Smolskaya , Evgeniia Leisi , Kseniya Barinova , Vladimir Muronetz

The interaction between different groups of amyloidogenic proteins is certainly involved in the development of neurodegenerative diseases, however, information about the role of such interactions is limited and contradictory. Of particular interest is the prion protein, individual fragments of which are formed in nerve tissues during proteolytic cleavage and can bind to alpha-synuclein, modeling its amyloid transformation in vivo. To investigate the role of individual domains of the prion protein (PrP) in regulating its own amyloid transformation, as well as alpha-synuclein fibrillation, we isolated PrP N- and C-terminal fragments (serine residue +23–124 aa and 103–234 aa, respectively) and studied their properties. The isolated C-terminal fragment formed more beta structures than the full-length protein, but at the same time, the efficiency of the fragment to form amyloid fibrils was reduced probably due to the dimensional issues. The N-terminal fragment of PrP not only did not form fibrillar structures, but also prevented amyloid transformation of full-length PrP. However, the PrP N-terminal fragment as well as prion protein monomers and mature fibrils’ particles had the opposite effect on the transformation of wild-type alpha-synuclein and its mutant form A53T, significantly reducing the lag phase of the aggregation. As a result, the heterogeneous small-sized aggregates were formed instead of large structured fibrils. This study discusses the fundamental possibility of using N-terminal fragments of PrP to prevent amyloidogenic transformation of full-length prion protein, along with the impact of proteolytic cleavage of PrP in vivo on the development of prion diseases and synucleinopathies.

不同组淀粉样蛋白之间的相互作用肯定参与了神经退行性疾病的发展，然而，关于这种相互作用的作用的信息是有限和矛盾的。特别令人感兴趣的是朊病毒蛋白，它的单个片段在蛋白水解裂解过程中在神经组织中形成，可以与α -突触核蛋白结合，模拟其在体内的淀粉样蛋白转化。为了研究朊蛋白（PrP）的单个结构域在调节其自身淀粉样蛋白转化以及α -突触核蛋白纤颤中的作用，我们分离了PrP N端和c端片段（分别为+23-124 aa和103-234 aa的丝氨酸残基）并研究了它们的性质。与全长蛋白相比，分离的c端片段形成了更多的β结构，但与此同时，片段形成淀粉样原纤维的效率可能由于尺寸问题而降低。PrP的n端片段不仅不形成纤维状结构，而且阻止了全长PrP的淀粉样蛋白转化。然而，PrP n端片段以及朊蛋白单体和成熟原纤维颗粒对野生型α -突触核蛋白及其突变体A53T的转化具有相反的作用，显著降低了聚集的滞后期。结果，形成了不均匀的小尺寸聚集体，而不是大结构的原纤维。本研究探讨了利用PrP的n端片段阻止全长朊病毒蛋白淀粉样转化的基本可能性，以及PrP在体内蛋白水解裂解对朊病毒疾病和突触核蛋白病发展的影响。

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引用次数: 0

MicroRNA expression profiling of white adipose tissue in the torpor response of the house mouse (Mus musculus) 家鼠（小家鼠）冬眠反应中白色脂肪组织的MicroRNA表达谱。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-16 DOI: 10.1016/j.biochi.2025.10.012

Yuhong Hu , Stuart R. Green , Ningmei Wang , Jing Zhang , Han Wang , Ziheng Zhao , Yue Gao , Kenneth B. Storey , Jingze Liu , Hui Wang

MicroRNAs (miRNAs), a critical class of short non-coding RNAs, regulate metabolic processes associated with mammalian torpor (e.g., Mus musculus), though their precise functional mechanisms remain incompletely characterized. Here, we employ RNA-seq to profile miRNA expression in white adipose tissue (WAT) of active versus torpid C57BL/6 mice. Among 863 detected miRNAs, 12 showed significant differential expression during torpor. In silico prediction of miRNA targets revealed these miRNAs preferentially target cancer-related pathways, indicating their potential role in suppressing cell proliferation during metabolic depression. Intriguingly, steroid biosynthesis genes escaped miRNA-mediated inhibition, suggesting active endocrine modulation by WAT during torpor. Machine learning helped to identify biomarkers for torpor in the mice, specifically a minimum of three miRNAs were sufficient to distinguish adipose samples from control versus torpid conditions. Taken together, this study demonstrates the role of miRNAs as transcriptional regulators of cell signalling pathways within WAT during mouse torpor.

MicroRNAs （miRNAs）是一类重要的短非编码rna，调节与哺乳动物（如小家鼠）冬眠相关的代谢过程，尽管其精确的功能机制尚未完全确定。在这里，我们使用RNA-seq分析了活跃和迟钝C57BL/6小鼠白色脂肪组织（WAT）中miRNA的表达。在863个检测到的mirna中，有12个在冬眠期间表现出显著的差异表达。miRNA靶点的计算机预测显示，这些miRNA优先靶向癌症相关通路，表明它们在代谢抑制期间抑制细胞增殖的潜在作用。有趣的是，类固醇生物合成基因逃脱了mirna介导的抑制，表明WAT在睡眠期间积极调节内分泌。机器学习有助于识别小鼠冬眠的生物标志物，特别是至少三个mirna足以区分对照组和冬眠条件下的脂肪样本。综上所述，本研究证明了mirna在小鼠冬眠期间作为WAT细胞信号通路的转录调节因子的作用。

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引用次数: 0

Revisiting SmE16, a calcium-binding protein from Schistosoma mansoni with unknown functions 重述来自曼氏血吸虫的一种功能未知的钙结合蛋白SmE16。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-08 DOI: 10.1016/j.biochi.2025.10.005

Thais Rangel Figueiredo , Miguel Eduardo Salazar Aurich , Amanda Toledo Machado , Luis Guilherme Mansor Basso , Ana Eliza Zeraik

Schistosoma mansoni is the causative agent of schistosomiasis, a disease that affects millions of people worldwide. Calcium signaling, essential for various parasite processes, emerges as a potential target. In this study, we focused on the calcium binding protein SmE16, initially identified as an egg-specific antigen from S. mansoni. However, our results indicate that SmE16 is a widely expressed protein, present across all developmental stages and tissues, with high expression in the adult worm's esophagus, evidenced by our in situ hybridization experiments. The recombinant protein was expressed in Escherichia coli and purified to assess its conformational change upon calcium binding. Biophysical analyses demonstrated that SmE16 undergoes significant structural alterations in the presence of calcium ions. Furthermore, calcium binding promotes partial oligomerization and significantly enhances the thermal stability of the protein. These structural changes are often associated with proteins recognized as calcium sensors, suggesting that SmE16 might play an active role in calcium-mediated signaling pathways. These findings highlight the importance of SmE16 in potential cellular signaling, paving the way for further research into its biological functions.

曼氏血吸虫是血吸虫病的病原体，这种疾病影响着全世界数百万人。钙信号是各种寄生虫过程所必需的，成为潜在的靶标。在这项研究中，我们重点研究了钙结合蛋白SmE16，该蛋白最初被鉴定为来自曼氏沙门氏菌的鸡蛋特异性抗原。然而，我们的研究结果表明，SmE16是一种广泛表达的蛋白，存在于所有发育阶段和组织中，在成虫的食道中有高表达，我们的原位杂交实验证明了这一点。重组蛋白在大肠杆菌中表达并纯化，以评估其在钙结合后的构象变化。生物物理分析表明，SmE16在钙离子存在下发生了显著的结构改变。此外，钙结合促进部分寡聚化，显著提高蛋白质的热稳定性。这些结构变化通常与被认为是钙传感器的蛋白质有关，这表明SmE16可能在钙介导的信号通路中发挥积极作用。这些发现强调了SmE16在潜在细胞信号传导中的重要性，为进一步研究其生物学功能铺平了道路。

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引用次数: 0

Deadly innovations: Molecular phylogenetics and evolution of phospholipase A2 toxins in viperid snake venoms 致命的创新：毒蛇毒液中磷脂酶A2毒素的分子系统发育和进化。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-18 DOI: 10.1016/j.biochi.2025.10.010

Lorenzo Seneci , Vivek Suranse , Marco Mancuso , Tobias Senoner , Bing Xie , Ivan Koludarov , Kartik Sunagar , Bryan G. Fry

Snake venoms have surged as model systems in evolutionary biology thanks to the dynamic diversification and accelerated evolution of many toxin families. Among these, phospholipase A₂ (PLA₂) constitute a prime example as they are ubiquitous across the venomous snake radiation and have evolved a wide variety of pathophysiological activities. This is especially true in vipers (family Viperidae), one of the most successful and medically significant venomous snake lineages worldwide. In this study, we gathered publicly available sequences of viper venom PLA₂s to recreate the molecular phylogeny and toxicological evolution of this toxin family to date. Furthermore, we determined the selection regimes regulating the evolution of these toxins with a comparative approach that combines multiple methodologies of phylogenetic reconstruction and analysis of selection signatures. Our phylogeny confirms the basal position of Asp49 PLA₂s (proteins with Asp at position 49), while derived clades, such as the non-enzymatic Lys49 myotoxins and the poorly characterised Ser49 type, are nested within. Neurotoxicity arose on multiple independent occasions (all within the Asp49 clade), with monomeric and dimeric forms only distantly related to each other. Positive Darwinian selection was widespread across the viper PLA₂ tree, in line with previous research. However, purifying selection was also preponderant (perhaps due to structural constraints imposed by the pathophysiological targets of these toxins) and relatively neutral substitutions were observed in certain clades. Overall, this study provides novel insights into the evolutionary history of viper venom PLA₂s through a comprehensive phylogenetic framework and highlights the need for complementary genomic and functional research into these toxins.

由于许多毒素家族的动态多样化和加速进化，蛇毒已成为进化生物学中的模型系统。其中，磷脂酶A2 （PLA2）是一个典型的例子，因为它们在毒蛇辐射中无处不在，并且已经进化出各种各样的病理生理活动。这在毒蛇（毒蛇科）中尤其如此，毒蛇是世界上最成功和医学上最重要的毒蛇血统之一。在这项研究中，我们收集了公开的毒蛇毒液PLA2s序列，以重建迄今为止该毒素家族的分子系统发育和毒理学进化。此外，我们确定了选择制度调节这些毒素的进化与比较的方法，结合多种方法的系统发育重建和选择特征分析。我们的系统发育证实了Asp49 PLA2s的基础位置（Asp位于49位的蛋白质），而衍生分支，如非酶促Lys49肌毒素和特征不佳的Ser49型，则嵌套在其中。神经毒性出现在多个独立的场合（都在Asp49分支内），单体和二聚体形式彼此之间只有遥远的关系。积极的达尔文选择在毒蛇PLA2树中广泛存在，这与之前的研究一致。然而，净化选择也占优势（可能是由于这些毒素的病理生理目标所施加的结构限制），并且在某些进化枝中观察到相对中性的替代。总的来说，这项研究通过一个全面的系统发育框架为毒蛇毒液PLA2s的进化史提供了新的见解，并强调了对这些毒素进行补充基因组和功能研究的必要性。

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引用次数: 0

Altered hemostatic dynamics and its regulation in follicular microenvironment of women with polycystic ovary syndrome 多囊卵巢综合征妇女的止血动力学改变及其对卵泡微环境的调节。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-09-27 DOI: 10.1016/j.biochi.2025.09.015

Roshan Dadachanji , Snehal Bhingardeve , Sadhana K. Desai , Vijay Mangoli , Srabani Mukherjee

Polycystic ovary syndrome (PCOS), presents with gynecological and metabolic issues such as anovulatory infertility, insulin resistance, hyperandrogenism, and obesity, and long-term cardiometabolic risks. Emerging evidence highlights coagulation–fibrinolysis balance influences essential ovarian functions, including ovulation, corpus luteum function, granulosa cell luteinization, and ECM remodeling. This study explores the relatively understudied coagulation and fibrinolytic factors in the ovarian microenvironment in Indian women. This case-control study examined the hemostatic potential of the follicular microenvironment in PCOS (n = 35) and controls (n = 30) by analyzing coagulation and fibrinolytic profiles in follicular fluid (FF), and granulosa cells (GCs). We observed significantly reduced transcript expressions of fibrinolytic factors including serine proteinase inhibitor (SERPINE1), tissue-type plasminogen activator (PLAT), coagulation factor fibrinogen gamma (FGG) in PCOS GCs. Conversely, transcript levels of thrombomodulin (THBD) and urokinase plasminogen activator receptor (PLAUR) were significantly higher in GCs of PCOS women compared to controls. Levels of both plasminogen activators, PLAT and PLAU, along with anticoagulant proteins, tissue factor pathway inhibitor and protein S were markedly declined, while plasminogen, THBD and histidine rich glycoprotein levels were significantly raised in FF of women with PCOS. Further, the construction of miRNA-mRNA regulatory network suggested that miRNAs may also be involved in hemostatic regulation in follicle microenvironment of PCOS. Our study showed that altered profiles of coagulation and fibrinolysis factors within follicular microenvironment of PCOS could contribute to disrupted hemostatic balance, mainly evidenced by compromised fibrinolysis. This may have significant implications for ovulatory dysfunction due to altered rupture, ECM remodeling and cumulus expansion in affected women.

多囊卵巢综合征（PCOS），表现为妇科和代谢问题，如无排卵性不孕、胰岛素抵抗、高雄激素症和肥胖，以及长期的心脏代谢风险。新出现的证据表明，凝血-纤溶平衡影响卵巢基本功能，包括排卵、黄体功能、颗粒细胞黄体化和ECM重塑。本研究探讨了印度女性卵巢微环境中相对未被充分研究的凝血和纤溶因子。本病例对照研究通过分析卵泡液（FF）和颗粒细胞（GCs）中的凝血和纤维蛋白溶解谱，检测了PCOS患者（35例）和对照组（30例）的卵泡微环境的止血潜能。我们观察到丝氨酸蛋白酶抑制剂（SERPINE1）、组织型纤溶酶原激活剂（PLAT）、凝血因子纤维蛋白原γ (FGG)等纤维蛋白溶解因子在PCOS GCs中的转录表达显著降低。相反，血栓调节素（THBD）和尿激酶纤溶酶原激活物受体（PLAUR）的转录水平在PCOS女性的GCs中显著高于对照组。PCOS女性FF中纤溶酶原激活剂PLAT和PLAU水平以及抗凝蛋白、组织因子途径抑制剂和蛋白S水平均明显下降，而纤溶酶原、THBD和富组氨酸糖蛋白水平显著升高。此外，miRNA-mRNA调控网络的构建提示mirna也可能参与PCOS卵泡微环境的止血调节。我们的研究表明，多囊卵巢综合征的卵泡微环境中凝血和纤溶因子的改变可能导致止血平衡被破坏，主要表现为纤维蛋白溶解功能受损。这可能对受影响妇女因破裂改变、ECM重塑和积云扩张而导致的排卵功能障碍具有重要意义。

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引用次数: 0

Isoform switching in the CD44/ESRP1 axis as a driver of EMT and cancer stemness across tumor types 从同种异构体到侵袭——cd44 / esrp1同种异构体转换如何驱动转移和癌症的发生。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-21 DOI: 10.1016/j.biochi.2025.10.015

K. Jankowska , W. Wójtowicz , M. Wierzbinka , K. Raszczok , K. Bajdak-Rusinek

Alternative splicing of cluster of differentiation 44 (CD44), regulated by epithelial splicing regulatory protein 1 (ESRP1), plays a critical role in cancer progression. The switch between CD44 variant (CD44v) and standard (CD44s) isoforms is tightly linked to epithelial–mesenchymal transition (EMT), metastatic potential and cancer stem cell (CSC) maintenance. This review integrates recent isoform-resolved findings to elucidate the molecular mechanisms underlying CD44/ESRP1-mediated splicing and its involvement in oncogenic signaling pathways promoting invasion, plasticity and therapy resistance. We also examine cancer-specific CD44 isoform expression patterns and assess their prognostic and therapeutic relevance. We propose that isoform-specific profiling of the CD44/ESRP1 axis may serve as a predictive framework for metastasis and therapy response, paving the way for targeted splicing-based therapeutics.

由上皮剪接调节蛋白1 （ESRP1）调控的CD44选择性剪接在癌症进展中起关键作用。CD44变体（CD44v）和标准（CD44s）亚型之间的转换与上皮-间质转化（EMT）、转移潜能和癌症干细胞（CSC）维持密切相关。这篇综述整合了最近的研究结果，阐明了CD44/ esrp1介导的剪接的分子机制及其在促进侵袭、可塑性和治疗抗性的致癌信号通路中的作用。我们还研究了癌症特异性CD44亚型表达模式，并评估其预后和治疗相关性。我们提出CD44/ESRP1轴的亚型特异性分析可以作为转移和治疗反应的预测框架，为靶向剪接治疗铺平道路。

引用次数: 0

DNA damage induces p53-dependent activation of the lncRNA TCERG1L-AS1 to regulate cell proliferation DNA损伤诱导p53依赖的lncRNA TCERG1L-AS1激活来调节细胞增殖。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 Epub Date: 2025-10-08 DOI: 10.1016/j.biochi.2025.10.002

Madhur Sharma , Nidhi Chourasia , Priyanka Priyanka , Debi Prasad Sarkar , Alo Nag , Sandeep Saxena

While long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators in stress responses, a systematic characterization of those regulated by p53 has remained incomplete. In this study, we adopted an integrative strategy that combined curated p53 ChIP-seq data with publicly available transcriptome profiles to identify lncRNAs potentially regulated by p53. Among these, we identified TCERG1L-AS1, a lncRNA whose promoter region contains canonical p53-binding motifs, as also demonstrated by luciferase reporter assays. TCERG1L-AS1 expression is specifically induced under genotoxic and oxidative stress, but not in response to metabolic stress, and its induction is dependent on functional p53. Functionally, enforced expression of TCERG1L-AS1 triggers G1-phase arrest and inhibits cellular proliferation and migration, as shown by flow cytometry, MTT, wound healing, and transwell migration assays. Transcriptome-wide analyses following TCERG1L-AS1 overexpression or silencing did not identify a consistent downstream effector, supporting emerging models in which certain lncRNAs act through indirect or scaffold-based mechanisms. Collectively, these findings establish TCERG1L-AS1 as a novel p53-regulated lncRNA with functional significance in tumor suppression and cellular stress responses.

虽然长链非编码rna （lncRNAs）越来越被认为是应激反应的关键调节因子，但对p53调控的长链非编码rna的系统表征仍然不完整。在这项研究中，我们采用了一种整合策略，将精心整理的p53 ChIP-seq数据与公开可用的转录组图谱相结合，以鉴定可能受p53调控的lncrna。其中，我们鉴定了TCERG1L-AS1，这是一种lncRNA，其启动子区域包含典型的p53结合基序，荧光素酶报告基因检测也证实了这一点。TCERG1L-AS1的表达在基因毒性和氧化应激下特异性诱导，但不响应代谢应激，其诱导依赖于功能p53。功能上，TCERG1L-AS1的强制表达触发g1期阻滞，抑制细胞增殖和迁移，流式细胞术、MTT、伤口愈合和transwell迁移实验表明。TCERG1L-AS1过表达或沉默后的转录组分析没有发现一致的下游效应，支持某些lncrna通过间接或基于支架的机制起作用的新兴模型。总之，这些发现证实了TCERG1L-AS1是一种新的p53调控lncRNA，在肿瘤抑制和细胞应激反应中具有重要的功能意义。

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引用次数: 0