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.
{"title":"Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis.","authors":"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","doi":"10.1186/s13062-024-00516-8","DOIUrl":"10.1186/s13062-024-00516-8","url":null,"abstract":"<p><strong>Background: </strong>TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"72"},"PeriodicalIF":5.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035292","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}
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.
{"title":"hsa_circ_0020093 suppresses ovarian cancer progression by modulating LRPPRC activity and miR-107/LATS2 signaling.","authors":"Yu Sun, Xiyi Chen, Yaqian Shi, Fang Teng, Chencheng Dai, Lili Ge, Juan Xu, Xuemei Jia","doi":"10.1186/s13062-024-00520-y","DOIUrl":"10.1186/s13062-024-00520-y","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"69"},"PeriodicalIF":5.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008333","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}
Pub Date : 2024-08-21DOI: 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。
{"title":"Novel crossover and recombination hotspots massively spread across primate genomes.","authors":"Mina Ohadi, Masoud Arabfard, Safoura Khamse, Samira Alizadeh, Sara Vafadar, Hadi Bayat, Nahid Tajeddin, Ali M A Maddi, Ahmad Delbari, Hamid R Khorram Khorshid","doi":"10.1186/s13062-024-00508-8","DOIUrl":"10.1186/s13062-024-00508-8","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"70"},"PeriodicalIF":5.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016341","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}
Pub Date : 2024-08-19DOI: 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.
{"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}
Pub Date : 2024-08-17DOI: 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.
{"title":"Breaking barriers: improving time and space resolution of arbuscular mycorrhizal symbiosis with single-cell sequencing approaches.","authors":"Sofía Cristina Somoza, Paola Bonfante, Marco Giovannetti","doi":"10.1186/s13062-024-00501-1","DOIUrl":"10.1186/s13062-024-00501-1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"67"},"PeriodicalIF":5.7,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995261","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}
Pub Date : 2024-08-16DOI: 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。
{"title":"A comprehensive molecular characterization of a claudin-low luminal B breast tumor.","authors":"Sara Giovannini, Artem Smirnov, Livia Concetti, Manuel Scimeca, Alessandro Mauriello, Julia Bischof, Valentina Rovella, Gerry Melino, Claudio Oreste Buonomo, Eleonora Candi, Francesca Bernassola","doi":"10.1186/s13062-024-00482-1","DOIUrl":"10.1186/s13062-024-00482-1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"66"},"PeriodicalIF":5.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995333","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}
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.
{"title":"Disulfidptosis signature predicts immune microenvironment and prognosis of gastric cancer.","authors":"Zitao Liu, Liang Sun, Wenjie Zhu, Jinfeng Zhu, Changlei Wu, Xingyu Peng, Huakai Tian, Chao Huang, Zhengming Zhu","doi":"10.1186/s13062-024-00518-6","DOIUrl":"10.1186/s13062-024-00518-6","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"65"},"PeriodicalIF":5.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987458","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}
Pub Date : 2024-08-08DOI: 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.
{"title":"Wandering about allostery.","authors":"Maurizio Brunori","doi":"10.1186/s13062-024-00502-0","DOIUrl":"10.1186/s13062-024-00502-0","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"64"},"PeriodicalIF":5.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900956","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}
Pub Date : 2024-08-07DOI: 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.
{"title":"Coordinating energy metabolism and signaling pathways in epithelial self-renewal and differentiation.","authors":"Maria Pia Polito, Alessio Romaldini, Serena Rinaldo, Elena Enzo","doi":"10.1186/s13062-024-00510-0","DOIUrl":"10.1186/s13062-024-00510-0","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"63"},"PeriodicalIF":5.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900955","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}
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.
{"title":"Neuregulin-4 protects cardiomyocytes against high-glucose-induced ferroptosis via the AMPK/NRF2 signalling pathway.","authors":"Pengfei Wang, Xiaohua Guo, Hongchao Wang, Lijie Wang, Meifang Ma, Bingyan Guo","doi":"10.1186/s13062-024-00505-x","DOIUrl":"10.1186/s13062-024-00505-x","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Nrg4 antagonizes high glucose-induced ferroptosis in cardiomyocytes via the AMPK/NRF2 signalling pathway.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"62"},"PeriodicalIF":5.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878402","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}