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Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis. 揭示 TSPAN7 在不同肿瘤中的独特作用:一项结合回顾性临床研究和生物信息学分析的泛癌症研究。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-22 DOI: 10.1186/s13062-024-00516-8
Bingnan Lu, Yifan Liu, Yuntao Yao, Dawei Zhu, Xiangmin Zhang, Keqin Dong, Xiao Xu, Donghao Lv, Zihui Zhao, Haoyu Zhang, Xinyue Yang, Wenjia Fu, Runzhi Huang, Jianwei Cao, Jian Chu, Xiuwu Pan, Xingang Cui

Background: TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear.

Methods: Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients' survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7.

Results: In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155-27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients' survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified.

Conclusion: TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level.

背景TSPAN7是肿瘤进展的一个重要因素。然而,TSPAN7的确切功能及其在泛癌症中的作用尚不清楚:方法:以新华队列中的 370 例肾脏肿瘤患者为研究对象,采用免疫组化方法对肿瘤组织和正常组织进行差异表达分析,探讨 TSPAN7 与患者生存的相关性。随后,我们进行了一项泛癌症研究,先后采用了差异表达分析、竞争性内源性 RNA(ceRNA)分析、蛋白-蛋白相互作用(PPI)分析,以及 TSPAN7 与临床特征、肿瘤纯度、肿瘤基因组学、肿瘤免疫和药物敏感性的相关性分析。最后,应用基因组富集分析确定了TSPAN7的富集通路:结果:在新华队列中,TSPAN7在肾脏肿瘤患者的肿瘤组织中表达明显上调(P值=0.0019)。TSPAN7的高表达与总生存期(OS)(P值=0.009)和无进展生存期(P值=0.009)的下降有关,并被进一步揭示为OS的独立危险因素(P值=0.0326,HR=5.66,95%CI=1.155-27.8)。在泛癌症分析中,TSPAN7在大多数肿瘤中表达下调,并且与患者生存、肿瘤纯度、肿瘤基因组学、肿瘤免疫和药物敏感性相关。此外,还构建了 TSPAN7 的 ceRNA 网络和 PPI 网络。最后,还确定了TSPAN7在各种肿瘤中的前五大富集通路:结论:TSPAN7是多种肿瘤,尤其是肾脏肿瘤的一种有前景的生物标记物,它与肿瘤纯度、肿瘤基因组学、肿瘤免疫学和泛癌水平的药物敏感性密切相关。
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引用次数: 0
hsa_circ_0020093 suppresses ovarian cancer progression by modulating LRPPRC activity and miR-107/LATS2 signaling. hsa_circ_0020093 通过调节 LRPPRC 活性和 miR-107/LATS2 信号传导抑制卵巢癌的进展。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-21 DOI: 10.1186/s13062-024-00520-y
Yu Sun, Xiyi Chen, Yaqian Shi, Fang Teng, Chencheng Dai, Lili Ge, Juan Xu, Xuemei Jia

A substantive body of evidence has demonstrated the significant roles of circular RNA (circRNA) in cancer. However, the contribution of dysregulated circRNAs to ovarian cancer (OC) remains elusive. We aim to elucidate the critical roles and mechanisms of hsa_circ_0020093, which was demonstrated to be downregulated in OC tissues in our previous study. In this study, we confirmed the decreased expression of hsa_circ_0020093 in OC tissues and cell lines and demonstrated the negative correlation between its expression and FIGO stage, abdominal implantation and CA125 level of OC patients. Through gain and loss of function studies, we confirmed the inhibitory role of hsa_circ_0020093 in ovarian tumor growth in vitro and in vivo. Mechanistically, based on the peri-nuclear accumulation of hsa_circ_0020093, we discovered the interaction between hsa_circ_0020093 and the mitochondrial protein LRPPRC by RNA pull-down, mass spectrometry, RNA Binding Protein Immunoprecipitation. As a result, qRT-PCR and transmission electron microscopy results showed that the mitochondria mRNA expression and mitochondria abundance were decreased upon hsa_circ_0020093-overexpression. Meanwhile, we also unearthed the hsa_circ_0020093/miR-107/LATS2 axis in OC according to RNA-sequencing, RIP and luciferase reporter assay data. Furthermore, LRPPRC and LATS2 are both reported as the upstream regulators of YAP, our study also studied the crosstalk between hsa_circ_0020093, LRPPRC and miR-107/LATS2, and unearthed the up-regulation of phosphorylated YAP in hsa_circ_0020093-overexpressing OC cells and xenograft tumors. Collectively, our study indicated the novel mechanism of hsa_circ_0020093 in suppressing OC progression through both hsa_circ_0020093/LRPPRC and hsa_circ_0020093/miR-107/LATS2 axes, providing a potential therapeutic target for OC patients.

大量证据表明,环状 RNA(circRNA)在癌症中发挥着重要作用。然而,调控失调的环状 RNA 对卵巢癌(OC)的影响仍然难以捉摸。我们旨在阐明 hsa_circ_0020093 的关键作用和机制。在本研究中,我们证实了 hsa_circ_0020093 在 OC 组织和细胞系中的表达下降,并证明了其表达与 OC 患者的 FIGO 分期、腹腔种植和 CA125 水平呈负相关。通过功能增益和丧失研究,我们证实了 hsa_circ_0020093 在体外和体内对卵巢肿瘤生长的抑制作用。从机理上讲,基于 hsa_circ_0020093 的核周积累,我们通过 RNA 拉取、质谱分析、RNA 结合蛋白免疫沉淀等方法发现了 hsa_circ_0020093 与线粒体蛋白 LRPPRC 之间的相互作用。结果,qRT-PCR 和透射电子显微镜结果表明,线粒体 mRNA 表达量和线粒体丰度在 hsa_circ_0020093 表达后均有所下降。同时,根据RNA测序、RIP和荧光素酶报告实验数据,我们还发现了OC中的hsa_circ_0020093/miR-107/LATS2轴。此外,LRPPRC和LATS2均被报道为YAP的上游调控因子,我们的研究还研究了hsa_circ_0020093、LRPPRC和miR-107/LATS2之间的相互影响,并发现了磷酸化YAP在hsa_circ_0020093过表达的OC细胞和异种移植肿瘤中的上调。总之,我们的研究表明了hsa_circ_0020093通过hsa_circ_0020093/LRPPRC和hsa_circ_0020093/miR-107/LATS2轴抑制OC进展的新机制,为OC患者提供了一个潜在的治疗靶点。
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引用次数: 0
Novel crossover and recombination hotspots massively spread across primate genomes. 新的交叉和重组热点大规模遍布灵长类动物基因组。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-21 DOI: 10.1186/s13062-024-00508-8
Mina Ohadi, Masoud Arabfard, Safoura Khamse, Samira Alizadeh, Sara Vafadar, Hadi Bayat, Nahid Tajeddin, Ali M A Maddi, Ahmad Delbari, Hamid R Khorram Khorshid

Background: The recombination landscape and subsequent natural selection have vast consequences forevolution and speciation. However, most of the crossover and recombination hotspots are yet to be discovered. We previously reported the relevance of C and G trinucleotide two-repeat units (CG-TTUs) in crossovers and recombination.

Methods: On a genome-wide scale, here we mapped all combinations of A and T trinucleotide two-repeat units (AT-TTUs) in human, consisting of AATAAT, ATAATA, ATTATT, TTATTA, TATTAT, and TAATAA. We also compared a number of the colonies formed by the AT-TTUs (distance between consecutive AT-TTUs < 500 bp) in several other primates and mouse.

Results: We found that the majority of the AT-TTUs (> 96%) resided in approximately 1.4 million colonies, spread throughout the human genome. In comparison to the CG-TTU colonies, the AT-TTU colonies were significantly more abundant and larger in size. Pure units and overlapping units of the pure units were readily detectable in the same colonies, signifying that the units were the sites of unequal crossover. We discovered dynamic sharedness of several of the colonies across the primate species studied, which mainly reached maximum complexity and size in human.

Conclusions: We report novel crossover and recombination hotspots of the finest molecular resolution, massively spread and shared across the genomes of human and several other primates. With respect to crossovers and recombination, these genomes are far more dynamic than previously envisioned.

背景:重组景观和随后的自然选择对生物进化和物种繁衍具有重大影响。然而,大多数交叉和重组热点尚未被发现。我们以前曾报道过 C 和 G 三核苷酸双重复单位(CG-TTUs)在交叉和重组中的相关性:在全基因组范围内,我们绘制了人类中 A 和 T 三核苷酸双重复单位(AT-TTU)的所有组合,包括 AATAAT、ATAATA、ATTATT、TTATTA、TATTAT 和 TAATAA。我们还比较了 AT-TTU 形成的菌落数(连续 AT-TTU 之间的距离):我们发现,大部分 AT-TTU (> 96%)分布在约 140 万个菌落中,遍布整个人类基因组。与 CG-TTU 群体相比,AT-TTU 群体明显更多,规模也更大。在同一菌落中很容易检测到纯合单元和纯合单元的重叠单元,这表明这些单元是不平等交叉的位点。我们发现,在所研究的灵长类物种中,有几个菌落具有动态共享性,主要是在人类中达到了最大的复杂性和规模:我们报告了具有最精细分子分辨率的新型交叉和重组热点,它们在人类和其他几种灵长类动物的基因组中大规模分布和共享。在交叉和重组方面,这些基因组的动态性远远超过了之前的设想。
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引用次数: 0
METTL3 in cancer-associated fibroblasts-derived exosomes promotes the proliferation and metastasis and suppresses ferroptosis in colorectal cancer by eliciting ACSL3 m6A modification. 癌症相关成纤维细胞外泌体中的METTL3通过诱导ACSL3 m6A修饰,促进结直肠癌的增殖和转移,并抑制铁变态反应。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-19 DOI: 10.1186/s13062-024-00511-z
Hongtao Ren, Mincong Wang, Xiulong Ma, Lei An, Yuyan Guo, Hongbing Ma

Background: Cancer-associated fibroblasts (CAFs) have been reported that can affect cancer cell proliferation, metastasis, ferroptosis, and immune escape. METTL3-mediated N6-methyladenine (m6A) modification is involved in the tumorigenesis of colorectal cancer (CRC). Herein, we investigated whether METTL3-dependent m6A in CAFs-derived exosomes (exo) affected CRC progression.

Methods: qRT-PCR and western blotting analyses detected levels of mRNAs and proteins. Cell proliferation and metastasis were evaluated using MTT, colony formation, transwell, and wound healing assays, respectively. Cell ferroptosis was assessed by detecting cell viability and the levels of Fe+, reactive oxygen species, and glutathione after erastin treatment. Exosomes were isolated from CAFs by ultracentrifugation. The m6A modification profile was determined by methylated RNA immunoprecipitation assay and the interaction between METTL3 and ACSL3 (acyl-CoA synthetase 3) was verified using dual-luciferase reporter assay. Animal models were established for in vivo analysis.

Results: CAFs promoted CRC cell proliferation and metastasis, and suppressed cell ferroptosis. METTL3 was enriched in CAFs and was packaged into exosomes. The m6A modification and METTL3 expression were increased in CRC samples. Knockdown of METTL3 in CAFs-exo suppressed CRC cell proliferation and metastasis, and induced cell ferroptosis. Mechanistically, METTL3 induced ACSL3 m6A modification and stabilized its expression. The anticancer effects mediated by METTL3-silenced CAFs-exo could be rescued by ACSL3 overexpression. Moreover, in vivo assay also showed that CAFs-exo with decreased METTL3 could hinder CRC growth and metastasis in mice models.

Conclusion: CAFs promoted the proliferation and metastasis, and restrained the ferroptosis in CRC by exosomal METTL3-elicited ACSL3 m6A modification.

背景:据报道,癌症相关成纤维细胞(CAFs)可影响癌细胞增殖、转移、铁变态反应和免疫逃逸。METTL3介导的N6-甲基腺嘌呤(m6A)修饰参与了结直肠癌(CRC)的肿瘤发生。方法:qRT-PCR 和 Western 印迹分析检测 mRNA 和蛋白质的水平。分别使用 MTT、菌落形成、transwell 和伤口愈合试验评估细胞增殖和转移。通过检测依拉斯汀处理后细胞的存活率以及铁+、活性氧和谷胱甘肽的水平来评估细胞的铁变态反应。通过超速离心从 CAFs 中分离出外泌体。通过甲基化 RNA 免疫沉淀分析确定了 m6A 修饰概况,并通过双荧光素酶报告分析验证了 METTL3 与 ACSL3(酰基-CoA 合成酶 3)之间的相互作用。建立动物模型进行体内分析:结果:CAFs促进了CRC细胞的增殖和转移,并抑制了细胞的铁凋亡。METTL3在CAFs中富集,并被包装成外泌体。在 CRC 样本中,m6A 修饰和 METTL3 表达增加。在CAFs-exo中敲除METTL3可抑制CRC细胞的增殖和转移,并诱导细胞铁凋亡。从机制上讲,METTL3能诱导ACSL3 m6A修饰并稳定其表达。METTL3沉默的CAFs-exo所介导的抗癌作用可以通过ACSL3的过表达得到挽救。此外,体内试验也表明,METTL3减弱的CAFs-exo可阻碍小鼠模型中的CRC生长和转移:结论:CAFs通过外泌体METTL3诱导的ACSL3 m6A修饰促进了CRC的增殖和转移,并抑制了其铁变态反应。
{"title":"METTL3 in cancer-associated fibroblasts-derived exosomes promotes the proliferation and metastasis and suppresses ferroptosis in colorectal cancer by eliciting ACSL3 m6A modification.","authors":"Hongtao Ren, Mincong Wang, Xiulong Ma, Lei An, Yuyan Guo, Hongbing Ma","doi":"10.1186/s13062-024-00511-z","DOIUrl":"10.1186/s13062-024-00511-z","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts (CAFs) have been reported that can affect cancer cell proliferation, metastasis, ferroptosis, and immune escape. METTL3-mediated N6-methyladenine (m6A) modification is involved in the tumorigenesis of colorectal cancer (CRC). Herein, we investigated whether METTL3-dependent m6A in CAFs-derived exosomes (exo) affected CRC progression.</p><p><strong>Methods: </strong>qRT-PCR and western blotting analyses detected levels of mRNAs and proteins. Cell proliferation and metastasis were evaluated using MTT, colony formation, transwell, and wound healing assays, respectively. Cell ferroptosis was assessed by detecting cell viability and the levels of Fe+, reactive oxygen species, and glutathione after erastin treatment. Exosomes were isolated from CAFs by ultracentrifugation. The m6A modification profile was determined by methylated RNA immunoprecipitation assay and the interaction between METTL3 and ACSL3 (acyl-CoA synthetase 3) was verified using dual-luciferase reporter assay. Animal models were established for in vivo analysis.</p><p><strong>Results: </strong>CAFs promoted CRC cell proliferation and metastasis, and suppressed cell ferroptosis. METTL3 was enriched in CAFs and was packaged into exosomes. The m6A modification and METTL3 expression were increased in CRC samples. Knockdown of METTL3 in CAFs-exo suppressed CRC cell proliferation and metastasis, and induced cell ferroptosis. Mechanistically, METTL3 induced ACSL3 m6A modification and stabilized its expression. The anticancer effects mediated by METTL3-silenced CAFs-exo could be rescued by ACSL3 overexpression. Moreover, in vivo assay also showed that CAFs-exo with decreased METTL3 could hinder CRC growth and metastasis in mice models.</p><p><strong>Conclusion: </strong>CAFs promoted the proliferation and metastasis, and restrained the ferroptosis in CRC by exosomal METTL3-elicited ACSL3 m6A modification.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"68"},"PeriodicalIF":5.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Breaking barriers: improving time and space resolution of arbuscular mycorrhizal symbiosis with single-cell sequencing approaches. 打破障碍:利用单细胞测序方法提高假根菌根共生的时空分辨率。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-17 DOI: 10.1186/s13062-024-00501-1
Sofía Cristina Somoza, Paola Bonfante, Marco Giovannetti

The cell and molecular bases of arbuscular mycorrhizal (AM) symbiosis, a crucial plant-fungal interaction for nutrient acquisition, have been extensively investigated by coupling traditional RNA sequencing techniques of roots sampled in bulk, with methods to capture subsets of cells such as laser microdissection. These approaches have revealed central regulators of this complex relationship, yet the requisite level of detail to effectively untangle the intricacies of temporal and spatial development remains elusive.The recent adoption of single-cell RNA sequencing (scRNA-seq) techniques in plant research is revolutionizing our ability to dissect the intricate transcriptional profiles of plant-microbe interactions, offering unparalleled insights into the diversity and dynamics of individual cells during symbiosis. The isolation of plant cells is particularly challenging due to the presence of cell walls, leading plant researchers to widely adopt nuclei isolation methods. Despite the increased resolution that single-cell analyses offer, it also comes at the cost of spatial perspective, hence, it is necessary the integration of these approaches with spatial transcriptomics to obtain a comprehensive overview.To date, few single-cell studies on plant-microbe interactions have been published, most of which provide high-resolution cell atlases that will become crucial for fully deciphering symbiotic interactions and addressing future questions. In AM symbiosis research, key processes such as the mutual recognition of partners during arbuscule development within cortical cells, or arbuscule senescence and degeneration, remain poorly understood, and these advancements are expected to shed light on these processes and contribute to a deeper understanding of this plant-fungal interaction.

根瘤菌共生是植物与真菌之间获取养分的重要互动关系,通过对根系进行大量取样的传统 RNA 测序技术与激光显微切割等捕获细胞子集的方法相结合,对根瘤菌共生的细胞和分子基础进行了广泛研究。最近在植物研究中采用的单细胞 RNA 测序(scRNA-seq)技术正在彻底改变我们剖析植物与微生物相互作用的复杂转录图谱的能力,为我们提供了对共生过程中单个细胞的多样性和动态的无与伦比的洞察力。由于细胞壁的存在,植物细胞的分离尤其具有挑战性,因此植物研究人员广泛采用细胞核分离方法。尽管单细胞分析提高了分辨率,但也付出了空间视角的代价,因此有必要将这些方法与空间转录组学结合起来,以获得全面的概述。迄今为止,有关植物与微生物相互作用的单细胞研究很少发表,其中大多数都提供了高分辨率的细胞图谱,这将成为全面解密共生相互作用和解决未来问题的关键。在AM共生研究中,诸如在皮层细胞内轴突发育过程中伙伴间的相互识别或轴突衰老和退化等关键过程仍然鲜为人知,这些进展有望揭示这些过程,并有助于加深对这种植物-真菌相互作用的理解。
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引用次数: 0
A comprehensive molecular characterization of a claudin-low luminal B breast tumor. 低腔隙 B 型乳腺肿瘤的综合分子特征。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-16 DOI: 10.1186/s13062-024-00482-1
Sara Giovannini, Artem Smirnov, Livia Concetti, Manuel Scimeca, Alessandro Mauriello, Julia Bischof, Valentina Rovella, Gerry Melino, Claudio Oreste Buonomo, Eleonora Candi, Francesca Bernassola

Breast cancer is the most common cause of death from cancer in women. Here, we present the case of a 43-year-old woman, who received a diagnosis of claudin-low luminal B breast cancer. The lesion revealed to be a poorly differentiated high-grade infiltrating ductal carcinoma, which was strongly estrogen receptor (ER)/progesterone receptor (PR) positive and human epidermal growth factor receptor (HER2) negative. Her tumor underwent in-depth chromosomal, mutational and gene expression analyses. We found a pathogenic protein truncating mutation in the TP53 gene, which is predicted to disrupt its transcriptional activity. The patient also harbors germline mutations in some mismatch repair (MMR) genes, and her tumor displays the presence of immune infiltrates, high tumor mutational burden (TMB) status and the apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) associated signatures, which, overall, are predictive for the use of immunotherapy. Here, we propose promising prognostic indicators as well as potential therapeutic strategies based on the molecular characterization of the tumor.

乳腺癌是女性最常见的癌症死因。在此,我们介绍了一名 43 岁女性的病例,她被诊断为低腔隙 B 型乳腺癌。病变为分化较差的高级别浸润性导管癌,雌激素受体(ER)/孕激素受体(PR)强阳性,人表皮生长因子受体(HER2)阴性。我们对她的肿瘤进行了深入的染色体、突变和基因表达分析。我们在 TP53 基因中发现了一个致病蛋白截断突变,预计会破坏其转录活性。该患者还携带一些错配修复(MMR)基因的种系突变,她的肿瘤显示出免疫浸润、高肿瘤突变负荷(TMB)状态和载脂蛋白 B mRNA 编辑酶催化多肽 3(APOBEC3)相关特征,总体而言,这些特征可预测免疫疗法的使用。在此,我们根据肿瘤的分子特征,提出了有前景的预后指标和潜在的治疗策略。
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引用次数: 0
Disulfidptosis signature predicts immune microenvironment and prognosis of gastric cancer. 二硫化硫特征可预测胃癌的免疫微环境和预后。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-15 DOI: 10.1186/s13062-024-00518-6
Zitao Liu, Liang Sun, Wenjie Zhu, Jinfeng Zhu, Changlei Wu, Xingyu Peng, Huakai Tian, Chao Huang, Zhengming Zhu

Background: Disulfidptosis is a newly identified mechanism of cell death triggered by disulfide stress. Thus, gaining a comprehensive understanding of the disulfidptosis signature present in gastric cancer (GC) could greatly enhance the development of personalized treatment strategies for this disease.

Methods: We employed consensus clustering to identify various subtypes of disulfidptosis and examined the distinct tumor microenvironment (TME) associated with each subtype. The Disulfidptosis (Dis) score was used to quantify the subtype of disulfidptosis in each patient. Subsequently, we assessed the predictive value of Dis score in terms of GC prognosis and immune efficacy. Finally, we conducted in vitro experiments to explore the impact of Collagen X (COL10A1) on the progression of GC.

Results: Two disulfidptosis-associated molecular subtypes (Discluster A and B) were identified, each with distinct prognosis, tumor microenvironment (TME), immune cell infiltration, and biological pathways. Discluster A, characterized by high expression of disulfidptosis genes, exhibited a high immune score but poor prognosis. Furthermore, the Dis score proved useful in predicting the prognosis and immune response in GC patients. Those in the low Dis score group showed better prognosis and increased sensitivity to immunotherapy. Finally, our experimental findings validated that downregulation of COL10A1 expression attenuates the proliferation and migration capabilities of GC cells while promoting apoptosis.

Conclusions: This study demonstrates that the disulfidptosis signature can assist in risk stratification and personalized treatment for patients with GC. The results offer valuable theoretical support for anti-tumor strategies.

背景:二硫化物跃迁是一种新发现的由二硫化物应激引发的细胞死亡机制。因此,全面了解胃癌(GC)中存在的二硫化硫特征可大大促进该疾病个性化治疗策略的开发:方法:我们采用共识聚类确定了各种二硫化硫亚型,并研究了与每种亚型相关的不同肿瘤微环境(TME)。二硫化血症(Dis)评分用于量化每位患者的二硫化血症亚型。随后,我们评估了 Dis 评分对 GC 预后和免疫效果的预测价值。最后,我们进行了体外实验,探讨胶原蛋白X(COL10A1)对GC进展的影响:结果:我们发现了两种与二硫化相关的分子亚型(Discluster A和B),它们的预后、肿瘤微环境(TME)、免疫细胞浸润和生物学途径各不相同。集群A以高表达二硫化基因为特征,免疫评分高,但预后较差。此外,Dis 评分还有助于预测 GC 患者的预后和免疫反应。低 Dis 评分组患者的预后较好,对免疫疗法的敏感性也较高。最后,我们的实验结果验证了下调 COL10A1 的表达可减轻 GC 细胞的增殖和迁移能力,同时促进细胞凋亡:本研究表明,二硫化氢特征有助于对 GC 患者进行风险分层和个性化治疗。研究结果为抗肿瘤策略提供了宝贵的理论支持。
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引用次数: 0
Wandering about allostery. 徘徊在allostery......
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-08 DOI: 10.1186/s13062-024-00502-0
Maurizio Brunori

It was a Lucky Strike to be working with Eraldo Antonini on hemoglobin and myoglobin when Jeffries Wyman arrived in Rome in 1961. I found myself connected with a number of creative scientists when the concept of allosteric control was conceived and gifted to the life science community. In retrospect, this was a demonstration of the skill and imagination of a few intelligent scientists that I happened to be close to. Those talents demonstrated the power of creativity as pictured by the motto "Mens agitat molem"; a celebration of humanism and intellect that paved the way to novel discoveries in the field of structure function relationships in proteins. I have presented hereby some of the events and the people as emerged from my memory over three decades of exciting scientific life.

1961 年,杰弗里斯-怀曼来到罗马,与埃拉尔多-安东尼尼(Eraldo Antonini)一起研究血红蛋白和肌红蛋白。我发现自己与许多富有创造力的科学家建立了联系,当时异位控制的概念被构想出来,并赠送给了生命科学界。现在回想起来,这展示了我碰巧亲近的几位聪明科学家的技能和想象力。正如 "Mens agitat molem "这一座右铭所描绘的那样,这些人才展现了创造力的力量;这是对人文精神和智慧的赞美,为蛋白质结构功能关系领域的新发现铺平了道路。在此,我将介绍我记忆中三十年精彩科学生活中的一些事件和人物。
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引用次数: 0
Coordinating energy metabolism and signaling pathways in epithelial self-renewal and differentiation. 协调上皮细胞自我更新和分化过程中的能量代谢和信号通路
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-07 DOI: 10.1186/s13062-024-00510-0
Maria Pia Polito, Alessio Romaldini, Serena Rinaldo, Elena Enzo

Epidermal stem cells (EPSCs) are essential for maintaining skin homeostasis and ensuring a proper wound healing. During in vitro cultivations, EPSCs give rise to transient amplifying progenitors and differentiated cells, finally forming a stratified epithelium that can be grafted onto patients. Epithelial grafts have been used in clinics to cure burned patients or patients affected by genetic diseases. The long-term success of these advanced therapies relies on the presence of a correct amount of EPSCs that guarantees long-term epithelial regeneration. For this reason, a deeper understanding of self-renewal and differentiation is fundamental to fostering their clinical applications.The coordination between energetic metabolism (e.g., glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and amino acid synthesis pathways), molecular signalling pathways (e.g., p63, YAP, FOXM1, AMPK/mTOR), and epigenetic modifications controls fundamental biological processes as proliferation, self-renewal, and differentiation. This review explores how these signalling and metabolic pathways are interconnected in the epithelial cells, highlighting the distinct metabolic demands and regulatory mechanisms involved in skin physiology.

表皮干细胞(EPSCs)对维持皮肤平衡和确保伤口正常愈合至关重要。在体外培养过程中,表皮干细胞可产生瞬时扩增的祖细胞和分化细胞,最终形成分层上皮细胞,并移植到患者身上。上皮细胞移植已被用于治疗烧伤患者或遗传病患者。这些先进疗法的长期成功有赖于正确数量的 EPSCs 的存在,从而保证上皮的长期再生。能量代谢(如糖酵解、三羧酸循环、氧化磷酸化和氨基酸合成途径)、分子信号途径(如 p63、YAP、FOXM1、AMPK/mTOR)和表观遗传修饰之间的协调控制着增殖、自我更新和分化等基本生物过程。本综述探讨了这些信号传导和新陈代谢途径在上皮细胞中的相互联系,重点介绍了皮肤生理学中不同的新陈代谢需求和调控机制。
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引用次数: 0
Neuregulin-4 protects cardiomyocytes against high-glucose-induced ferroptosis via the AMPK/NRF2 signalling pathway. Neuregulin-4通过AMPK/NRF2信号通路保护心肌细胞免受高血糖诱导的铁变态反应。
IF 5.7 2区 生物学 Q1 BIOLOGY Pub Date : 2024-08-02 DOI: 10.1186/s13062-024-00505-x
Pengfei Wang, Xiaohua Guo, Hongchao Wang, Lijie Wang, Meifang Ma, Bingyan Guo

Background: High glucose levels are key factors and key contributors to several cardiovascular diseases associated with cardiomyocyte injury. Ferroptosis, which was identified in recent years, is a mode of cell death caused by the iron-mediated accumulation of lipid peroxides. Neuregulin-4 (Nrg4) is an adipokine that has protective effects against metabolic disorders and insulin resistance. Our previous study revealed that Nrg4 has a protective effect against diabetic myocardial injury, and the aim of this study was to investigate whether Nrg4 could attenuate the occurrence of high glucose-induced ferroptosis in cardiomyocytes.

Methods: We constructed an in vivo diabetic myocardial injury model in which primary cardiomyocytes were cultured in vitro and treated with Nrg4. Changes in ferroptosis-related protein levels and ferroptosis-related indices in cardiomyocytes were observed. In addition, we performed back-validation and explored signalling pathways that regulate ferroptosis in primary cardiomyocytes.

Results: Nrg4 attenuated cardiomyocyte ferroptosis both in vivo and in vitro. Additionally, the AMPK/NRF2 signalling pathway was activated during this process, and when the AMPK/NRF2 pathway was inhibited, the beneficial effects of Nrg4 were attenuated.

Conclusion: Nrg4 antagonizes high glucose-induced ferroptosis in cardiomyocytes via the AMPK/NRF2 signalling pathway.

背景:高血糖是导致与心肌细胞损伤有关的多种心血管疾病的关键因素和重要诱因。近年来发现的铁过氧化是一种由铁介导的脂质过氧化物积累引起的细胞死亡模式。Neuregulin-4(Nrg4)是一种脂肪因子,对代谢紊乱和胰岛素抵抗具有保护作用。我们之前的研究发现,Nrg4 对糖尿病心肌损伤有保护作用,本研究旨在探讨 Nrg4 是否能减轻高糖诱导的心肌细胞铁变态反应的发生:方法:我们构建了一个体内糖尿病心肌损伤模型,在体外培养原代心肌细胞并用Nrg4处理。我们观察到了心肌细胞中与铁变态反应相关的蛋白水平和铁变态反应相关指数的变化。此外,我们还进行了反向验证,并探索了调控原代心肌细胞中铁细胞凋亡的信号通路:结果:Nrg4 在体内和体外均可减轻心肌细胞的铁突变。此外,在这一过程中,AMPK/NRF2 信号通路被激活,当 AMPK/NRF2 通路被抑制时,Nrg4 的有益作用就会减弱:结论:Nrg4可通过AMPK/NRF2信号通路拮抗高糖诱导的心肌细胞铁突变。
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Biology Direct
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