Pub Date : 2024-08-01Epub Date: 2023-11-20DOI: 10.1007/s10528-023-10556-w
Iftikhar Ahmed, Muhammad Muzammal, Muzammil Ahmad Khan, Hafiz Ullah, Arshad Farid, Muhammad Yasin, Jabbar Khan, Khurshid Alam, Asif Mir
Intellectual disability, a genetically and clinically varied disorder and is a significant health problem, particularly in less developed countries due to larger family size and high ratio of consanguineous marriages. In the current genetic study, we investigate and find the novel disease causative factors in the four Pakistani families with severe type of non-syndromic intellectual disability. For genetic analysis whole-exome sequencing (WES) and Sanger sequencing was performed. I-TASSER and Cluspro tools were used for Protein modeling and Protein-protein docking. Sanger sequencing confirms the segregation of novel homozygous variants in all the families i.e., c.245 T > C; p.Leu82Pro in SLC50A1 gene in family 1, missense variant c.1037G > A; p.Arg346His in TARS2 gene in family 2, in family 3 and 4, nonsense mutation c.234G > A; p.Trp78Term and missense mutation c.2200G > A; p.Asp734Asn in TBC1D3 and ANAPC2 gene, respectively. In silico functional studies have found the drastic effect of these mutations on protein structure and its interaction properties. Substituted amino acids were highly conserved and present on highly conserved region throughout the species. The discovery of pathogenic variants in SLC50A1, TARS2, TBC1D1 and ANAPC2 shows that the specific pathways connected with these genes may be important in cognitive impairment. The decisive role of pathogenic variants in these genes cannot be determined with certainty due to lack of functional data. However, exome sequencing and segregation analysis of all filtered variants revealed that the currently reported variants were the only variations from the respective families that segregated with the phenotype in the family.
{"title":"Identification of Four Novel Candidate Genes for Non-syndromic Intellectual Disability in Pakistani Families.","authors":"Iftikhar Ahmed, Muhammad Muzammal, Muzammil Ahmad Khan, Hafiz Ullah, Arshad Farid, Muhammad Yasin, Jabbar Khan, Khurshid Alam, Asif Mir","doi":"10.1007/s10528-023-10556-w","DOIUrl":"10.1007/s10528-023-10556-w","url":null,"abstract":"<p><p>Intellectual disability, a genetically and clinically varied disorder and is a significant health problem, particularly in less developed countries due to larger family size and high ratio of consanguineous marriages. In the current genetic study, we investigate and find the novel disease causative factors in the four Pakistani families with severe type of non-syndromic intellectual disability. For genetic analysis whole-exome sequencing (WES) and Sanger sequencing was performed. I-TASSER and Cluspro tools were used for Protein modeling and Protein-protein docking. Sanger sequencing confirms the segregation of novel homozygous variants in all the families i.e., c.245 T > C; p.Leu82Pro in SLC50A1 gene in family 1, missense variant c.1037G > A; p.Arg346His in TARS2 gene in family 2, in family 3 and 4, nonsense mutation c.234G > A; p.Trp78Term and missense mutation c.2200G > A; p.Asp734Asn in TBC1D3 and ANAPC2 gene, respectively. In silico functional studies have found the drastic effect of these mutations on protein structure and its interaction properties. Substituted amino acids were highly conserved and present on highly conserved region throughout the species. The discovery of pathogenic variants in SLC50A1, TARS2, TBC1D1 and ANAPC2 shows that the specific pathways connected with these genes may be important in cognitive impairment. The decisive role of pathogenic variants in these genes cannot be determined with certainty due to lack of functional data. However, exome sequencing and segregation analysis of all filtered variants revealed that the currently reported variants were the only variations from the respective families that segregated with the phenotype in the family.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-11-29DOI: 10.1007/s10528-023-10570-y
Xi Yang, Chun Feng, Donghui Jiang, Xin Xu, Yingying Zhang, Jin Wang, Xiaoguang He
Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor of head and neck. It was verified that circ0005027 was downregulated in HSCC tissues. Here, we aimed to investigate the function and specific regulatory mechanism of circ0005027 in HSCC. Ten pairs tissues of HSCC and adjacent para-cancer were collected. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) measured circ0005027, miR-548c-3p, and Cadherin 1 (CDH1) mRNA expression. CCK-8 analyzed cell proliferation viability. Flow cytometry assay detected cell cycle and apoptosis rate. Clonal formation assay measured the clonal ability. Transwell detected cell invasion ability. Western blot was performed to detect CDH1, LAST1, p-LAST1, MST1, p-MST1, YAP1, p-YAP1, TAZ and p-TAZ protein level. Dual-luciferase, RIP and RNA pull-down assay identified the target relationship among circ0005027, miR-548c-3p and CDH1. circ0005027 was decreased in tissues and FaDu cells of HSCC. Overexpression of circ0005027 inhibited cell viability, G1-S transition, clonal formation, and invasion and increased cell apoptosis. circ0005027 acted as a ceRNA and decreased circ0005027 enhanced the malignant process of FaDu cells through sponging miR-548c-3p and inhibiting CDH1 expression. Overexpression of CDH1 activated YAP1/TAZ pathway and inhibited the growth of HSCC in vitro. circ0005027 might act as a potential biomarker for the progression and prognosis prediction in HSCC by regulating miR-548c-3p/CDH1/ YAP1/TAZ signaling pathway.
{"title":"circ0005027 Acting as a ceRNA Affects the Malignant Biological Behavior of Hypopharyngeal Squamous Cell Carcinoma by Modulating miR-548c-3p/CDH1 Axis.","authors":"Xi Yang, Chun Feng, Donghui Jiang, Xin Xu, Yingying Zhang, Jin Wang, Xiaoguang He","doi":"10.1007/s10528-023-10570-y","DOIUrl":"10.1007/s10528-023-10570-y","url":null,"abstract":"<p><p>Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor of head and neck. It was verified that circ0005027 was downregulated in HSCC tissues. Here, we aimed to investigate the function and specific regulatory mechanism of circ0005027 in HSCC. Ten pairs tissues of HSCC and adjacent para-cancer were collected. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) measured circ0005027, miR-548c-3p, and Cadherin 1 (CDH1) mRNA expression. CCK-8 analyzed cell proliferation viability. Flow cytometry assay detected cell cycle and apoptosis rate. Clonal formation assay measured the clonal ability. Transwell detected cell invasion ability. Western blot was performed to detect CDH1, LAST1, p-LAST1, MST1, p-MST1, YAP1, p-YAP1, TAZ and p-TAZ protein level. Dual-luciferase, RIP and RNA pull-down assay identified the target relationship among circ0005027, miR-548c-3p and CDH1. circ0005027 was decreased in tissues and FaDu cells of HSCC. Overexpression of circ0005027 inhibited cell viability, G1-S transition, clonal formation, and invasion and increased cell apoptosis. circ0005027 acted as a ceRNA and decreased circ0005027 enhanced the malignant process of FaDu cells through sponging miR-548c-3p and inhibiting CDH1 expression. Overexpression of CDH1 activated YAP1/TAZ pathway and inhibited the growth of HSCC in vitro. circ0005027 might act as a potential biomarker for the progression and prognosis prediction in HSCC by regulating miR-548c-3p/CDH1/ YAP1/TAZ signaling pathway.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
COVID-19 (Coronavirus disease 2019) is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which can lead to pneumonia, cytokine storms, and lymphopenia. Patients with cancer are more susceptible to SARS-CoV-2 infection and severe COVID-19 due to immunosuppression. Recent studies have indicated that NRP1 (Neuropilin 1) may act as a novel mediator of SARS-CoV-2 entry into the host cell. As no systematic review has been performed investigating the characteristics of NRP1 in pan-carcinoma, we comprehensively analyzed NRP1 in patients with pan-cancer. Using a bioinformatics approach, we aimed to systematically examine NRP1 expression profiles in both pan-carcinoma and healthy tissues. We found that lung and genitourinary cancers have a relatively higher NRP-1 expression than other cancer patients, suggesting that these patients may be more susceptible to SARS-CoV-2. Our analysis further revealed that NRP1 expression was downregulated in Vero E6 cells, whole blood, lung organoids, testis tissue, and alveolospheres infected with SARS-CoV-2. Notably, NRP1 was associated with immune cell infiltration, immune checkpoint genes, and immune-related genes in most patients with cancer. These findings suggest that, in patients with specific types of cancer, especially lung and genitourinary, high expression of NRP1 contributes to greater susceptibility to SARS-CoV-2 infection and an increased risk of damage due to cytokine storms. Overall, NRP1 appears to play a critical role in regulating immunological properties and metabolism in many tumor types. Specific inhibitors of the NRP1 antigen (pegaptanib, EG00229, or MNRP1685A) combined with other anti-SARS-CoV-2 strategies may aid in treating patients with lung and genitourinary cancers following SARS-CoV-2 infection.
{"title":"A Comprehensive Analysis of NRP1 in Malignancies Provide Therapeutic Implication for Treating Cancer Patients Infected with SARS-CoV-2.","authors":"Shuzhao Chen, Limei Zhang, Yiling Song, Kunying Xie, Yun Wang, Yang Liang","doi":"10.1007/s10528-023-10518-2","DOIUrl":"10.1007/s10528-023-10518-2","url":null,"abstract":"<p><p>COVID-19 (Coronavirus disease 2019) is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which can lead to pneumonia, cytokine storms, and lymphopenia. Patients with cancer are more susceptible to SARS-CoV-2 infection and severe COVID-19 due to immunosuppression. Recent studies have indicated that NRP1 (Neuropilin 1) may act as a novel mediator of SARS-CoV-2 entry into the host cell. As no systematic review has been performed investigating the characteristics of NRP1 in pan-carcinoma, we comprehensively analyzed NRP1 in patients with pan-cancer. Using a bioinformatics approach, we aimed to systematically examine NRP1 expression profiles in both pan-carcinoma and healthy tissues. We found that lung and genitourinary cancers have a relatively higher NRP-1 expression than other cancer patients, suggesting that these patients may be more susceptible to SARS-CoV-2. Our analysis further revealed that NRP1 expression was downregulated in Vero E6 cells, whole blood, lung organoids, testis tissue, and alveolospheres infected with SARS-CoV-2. Notably, NRP1 was associated with immune cell infiltration, immune checkpoint genes, and immune-related genes in most patients with cancer. These findings suggest that, in patients with specific types of cancer, especially lung and genitourinary, high expression of NRP1 contributes to greater susceptibility to SARS-CoV-2 infection and an increased risk of damage due to cytokine storms. Overall, NRP1 appears to play a critical role in regulating immunological properties and metabolism in many tumor types. Specific inhibitors of the NRP1 antigen (pegaptanib, EG00229, or MNRP1685A) combined with other anti-SARS-CoV-2 strategies may aid in treating patients with lung and genitourinary cancers following SARS-CoV-2 infection.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by arachnodactyly, multiple joint contractures, progressive kyphoscoliosis, pectus deformity and abnormal crumpled ears. FBN2 is the only gene currently known to be associated with CCA. In this study, we report on a prenatal case presented with skeletal, cardiac and spinal malformations. And his father had elongated limbs, contractures of the proximal interphalangeal joints, high myopia and scoliosis. We conducted whole exome sequencing (WES) on the fetus-parental trio and a heterozygous variant (hg19 chr5:127,673,685, c.3598 + 4A > G, NM_001999.4) in intron 27 of the FBN2 gene was successfully identified, inherited from the father. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (126 bp) by disrupting the splice-donor site and destroyed the 17th calcium-binding epidermal growth factor-like (cbEGF) domain. Our research not only finds the etiology of the disease in affected individuals and expands the mutation spectrum of FBN2 gene, but also provides genetic counseling and fertility guidance for this family.
{"title":"A Novel Splice Site Mutation in the FBN2 Gene in a Chinese Family with Congenital Contractural Arachnodactyly.","authors":"Cuiping Zhang, Fengchang Qiao, Qing Cheng, Chunyu Luo, Qinxin Zhang, Ping Hu, Zhengfeng Xu","doi":"10.1007/s10528-023-10550-2","DOIUrl":"10.1007/s10528-023-10550-2","url":null,"abstract":"<p><p>Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by arachnodactyly, multiple joint contractures, progressive kyphoscoliosis, pectus deformity and abnormal crumpled ears. FBN2 is the only gene currently known to be associated with CCA. In this study, we report on a prenatal case presented with skeletal, cardiac and spinal malformations. And his father had elongated limbs, contractures of the proximal interphalangeal joints, high myopia and scoliosis. We conducted whole exome sequencing (WES) on the fetus-parental trio and a heterozygous variant (hg19 chr5:127,673,685, c.3598 + 4A > G, NM_001999.4) in intron 27 of the FBN2 gene was successfully identified, inherited from the father. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (126 bp) by disrupting the splice-donor site and destroyed the 17th calcium-binding epidermal growth factor-like (cbEGF) domain. Our research not only finds the etiology of the disease in affected individuals and expands the mutation spectrum of FBN2 gene, but also provides genetic counseling and fertility guidance for this family.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 : 2024-08-01Epub Date: 2023-11-24DOI: 10.1007/s10528-023-10567-7
Pengguo Xia, Yan Zhang, Xuemin Zhang
The dehydration response element-binding (DREB) transcription factor is a subfamily of AP2/ERF. It actively responds to various abiotic stresses in plants. As one of the representative plants, Panax notoginseng is sensitive to Nitrogen (N). Here, bioinformatics analysis, the identification, chromosomal location, phylogeny, structure, cis-acting elements, and collinearity of PnDREBs were analyzed. In addition, the expression levels of PnDREBs were analyzed by quantitative reverse transcription PCR. In this study, 54 PnDREBs were identified and defined as PnDREB1 to PnDREB54. They were divided into 6 subfamilies (A1-A6). And 44 PnDREBs were irregularly distributed on 10 of 12 chromosomes. Each group showed specific motifs and exon-intron structures. By predicting cis-acting elements, the PnDREBs may participate in biotic stress, abiotic stress, and hormone induction. Collinear analysis showed that fragment duplication events were beneficial to the amplification and evolution of PnDREB members. The expression of PnDREBs showed obvious tissue specificity in its roots, flowers, and leaves. In addition, under the action of ammonium nitrogen and nitrate nitrogen at the 15 mM level, the level of PnDREB genes expression in roots varied to different degrees. In this study, we identified and characterized PnDREBs for the first time, and analyzed that PnDREBs may be related to the response of P. Notoginseng to N sensitiveness. The results of this study lay a foundation for further research on the function of PnDREBs in P. Notoginseng.
{"title":"The Potential Relevance of PnDREBs to Panax notoginseng Nitrogen Sensitiveness.","authors":"Pengguo Xia, Yan Zhang, Xuemin Zhang","doi":"10.1007/s10528-023-10567-7","DOIUrl":"10.1007/s10528-023-10567-7","url":null,"abstract":"<p><p>The dehydration response element-binding (DREB) transcription factor is a subfamily of AP2/ERF. It actively responds to various abiotic stresses in plants. As one of the representative plants, Panax notoginseng is sensitive to Nitrogen (N). Here, bioinformatics analysis, the identification, chromosomal location, phylogeny, structure, cis-acting elements, and collinearity of PnDREBs were analyzed. In addition, the expression levels of PnDREBs were analyzed by quantitative reverse transcription PCR. In this study, 54 PnDREBs were identified and defined as PnDREB1 to PnDREB54. They were divided into 6 subfamilies (A1-A6). And 44 PnDREBs were irregularly distributed on 10 of 12 chromosomes. Each group showed specific motifs and exon-intron structures. By predicting cis-acting elements, the PnDREBs may participate in biotic stress, abiotic stress, and hormone induction. Collinear analysis showed that fragment duplication events were beneficial to the amplification and evolution of PnDREB members. The expression of PnDREBs showed obvious tissue specificity in its roots, flowers, and leaves. In addition, under the action of ammonium nitrogen and nitrate nitrogen at the 15 mM level, the level of PnDREB genes expression in roots varied to different degrees. In this study, we identified and characterized PnDREBs for the first time, and analyzed that PnDREBs may be related to the response of P. Notoginseng to N sensitiveness. The results of this study lay a foundation for further research on the function of PnDREBs in P. Notoginseng.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-12-05DOI: 10.1007/s10528-023-10584-6
Bao-Jin Chi, Zhong-Lei Duan, Al-Kamel Haithm Ali Mohammed Hasan, Xing-Zhong Yin, Bo-Yang Cui, Fang-Fang Wang
Bladder cancer (BCa), which usually occurs in bladder epithelial cells and is the fifth most common type of cancer in the world. he recurrence rate within 5 years after surgery is 0.8-45% of patients with early bladder cancer. Therefore, finding appropriate drug therapy for patients with bladder cancer can provide a reference for clinical treatment and play an important role in improving the prognosis of patients. In this study, CCK8 assay result showed that the inhibition of bladder cancer cell activity by Curdione and GEM increased with time and dose. Subsequently, CCK8, clone formation assay and Transwell result showed Curdione enhances GEM inhibition of bladder cancer cell activity, clonal formation and migration, these combine therapeutic schedule also could inhibited growth of in vivo xenograft tumors. The comprehensive database showed that CA2 is a potential target genes of Curdione, and Knockdown CA2 enhances GEM induced inhibition of cell proliferation and migration. Based on these advantages, Curdione may be a new type of action drug or adjunct for the treatment of bladder cancer.
{"title":"Effect and Mechanism of Curdione Combined with Gemcitabine on Migration and Invasion of Bladder Cancer.","authors":"Bao-Jin Chi, Zhong-Lei Duan, Al-Kamel Haithm Ali Mohammed Hasan, Xing-Zhong Yin, Bo-Yang Cui, Fang-Fang Wang","doi":"10.1007/s10528-023-10584-6","DOIUrl":"10.1007/s10528-023-10584-6","url":null,"abstract":"<p><p>Bladder cancer (BCa), which usually occurs in bladder epithelial cells and is the fifth most common type of cancer in the world. he recurrence rate within 5 years after surgery is 0.8-45% of patients with early bladder cancer. Therefore, finding appropriate drug therapy for patients with bladder cancer can provide a reference for clinical treatment and play an important role in improving the prognosis of patients. In this study, CCK8 assay result showed that the inhibition of bladder cancer cell activity by Curdione and GEM increased with time and dose. Subsequently, CCK8, clone formation assay and Transwell result showed Curdione enhances GEM inhibition of bladder cancer cell activity, clonal formation and migration, these combine therapeutic schedule also could inhibited growth of in vivo xenograft tumors. The comprehensive database showed that CA2 is a potential target genes of Curdione, and Knockdown CA2 enhances GEM induced inhibition of cell proliferation and migration. Based on these advantages, Curdione may be a new type of action drug or adjunct for the treatment of bladder cancer.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138481691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-11-29DOI: 10.1007/s10528-023-10583-7
Zhe Su, Wenjing Su, Chenglong Li, Peihui Ding, Kaixue Lao, Yiqian Li, Yanlin Wang
Endometriosis (EMT) is a prevalent gynecological disorder characterized by pain and infertility associated with the menstrual cycle. Pyroptosis, an emerging cell death mechanism, has been implicated in the pathogenesis of diverse diseases, highlighting its pivotal role in disease progression. Therefore, our study aimed to investigate the impact of pyroptosis in EMT using a comprehensive bioinformatics approach. We initially obtained two datasets from the Gene Expression Omnibus database and performed differential expression analysis to identify pyroptosis-related genes (PRGs) that were differentially expressed between EMT and non-EMT samples. Subsequently, several machine learning algorithms, namely least absolute shrinkage selection operator regression, support vector machine-recursive feature elimination, and random forest algorithms were used to identify a hub gene to construct an effective diagnostic model for EMT. Receiver operating characteristic curve analysis, nomogram, calibration curve, and decision curve analysis were applied to validate the performance of the model. Based on the selected hub gene, differential expression analysis between high- and low-expression groups was conducted to explore the functions and signaling pathways related to it. Additionally, the correlation between the hub gene and immune cells was investigated to gain insights into the immune microenvironment of EMT. Finally, a pyroptosis-related competing endogenous RNA network was constructed to elucidate the regulatory interactions of the hub gene. Our study revealed the potential contribution of a specific PRG to the pathogenesis of EMT, providing a novel perspective for clinical diagnosis and treatment of EMT.
{"title":"Identification and Immune Characteristics Study of Pyroptosis‑Related Genes in Endometriosis.","authors":"Zhe Su, Wenjing Su, Chenglong Li, Peihui Ding, Kaixue Lao, Yiqian Li, Yanlin Wang","doi":"10.1007/s10528-023-10583-7","DOIUrl":"10.1007/s10528-023-10583-7","url":null,"abstract":"<p><p>Endometriosis (EMT) is a prevalent gynecological disorder characterized by pain and infertility associated with the menstrual cycle. Pyroptosis, an emerging cell death mechanism, has been implicated in the pathogenesis of diverse diseases, highlighting its pivotal role in disease progression. Therefore, our study aimed to investigate the impact of pyroptosis in EMT using a comprehensive bioinformatics approach. We initially obtained two datasets from the Gene Expression Omnibus database and performed differential expression analysis to identify pyroptosis-related genes (PRGs) that were differentially expressed between EMT and non-EMT samples. Subsequently, several machine learning algorithms, namely least absolute shrinkage selection operator regression, support vector machine-recursive feature elimination, and random forest algorithms were used to identify a hub gene to construct an effective diagnostic model for EMT. Receiver operating characteristic curve analysis, nomogram, calibration curve, and decision curve analysis were applied to validate the performance of the model. Based on the selected hub gene, differential expression analysis between high- and low-expression groups was conducted to explore the functions and signaling pathways related to it. Additionally, the correlation between the hub gene and immune cells was investigated to gain insights into the immune microenvironment of EMT. Finally, a pyroptosis-related competing endogenous RNA network was constructed to elucidate the regulatory interactions of the hub gene. Our study revealed the potential contribution of a specific PRG to the pathogenesis of EMT, providing a novel perspective for clinical diagnosis and treatment of EMT.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Preeclampsia is the most common and serious complication of pregnancy. Variants of Sirtuin-1 (SIRT1) as a key player in the regulation of oxidant/antioxidant signaling pathways might be involved in the pathogenesis of preeclampsia. In the present case-control study 300 women with and without preeclampsia were studied for SIRT1 variants (rs7895833, rs7069102, and rs2273773) and haplotypes. Also, the relationship of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and Zn, Cu, and Se levels to the polymorphisms were investigated. The SIRT1 rs7895833 A > G, rs7069102 C > G, and the rs2273773 C > T polymorphisms were associated with the risk of preeclampsia. We found the haplotypes G (rs7895833) C (rs7069102) C (rs2273773), GCC, and ACC compared to the AGT decreased the risk of preeclampsia. The risk haplotype of AGT was associated with higher GPx activity compared to the GCC haplotype. A significantly higher level of Cu and lower levels of Zn and Se in patients with preeclampsia compared to controls were detected. Also, a significantly lower SOD and higher GPx activity in preeclamptic patients compared to controls were found. The three risk genotypes of AA (rs7895833), GG (rs7069102), and TT (rs2273773) significantly decreased the Zn level and SOD activity, and the TT genotype (rs2273773) increased the Cu level in all studied women. The presence of rs7069102 polymorphism was associated with enhanced systolic blood pressure. For the first time, we indicated three SIRT1 polymorphisms and the AGT haplotype are risk factors for preeclampsia development. Also, SIRT1 variants and haplotypes affect the levels of antioxidant enzymes and their cofactors, complicating the pregnancy outcome.
子痫前期是妊娠期最常见、最严重的并发症。Sirtuin-1 (SIRT1)的变异在氧化/抗氧化信号通路的调控中起关键作用,可能参与了子痫前期的发病机制。在本病例对照研究中,研究了300名患有和未患有先兆子痫的妇女的SIRT1变异(rs7895833、rs7069102和rs2273773)和单倍型。研究了谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)活性以及锌、铜、硒水平与基因多态性的关系。SIRT1 rs7895833 A > G、rs7069102 C > G和rs2273773 C > T多态性与子痫前期风险相关。我们发现单倍型G (rs7895833) C (rs7069102) C (rs2273773)、GCC和ACC与AGT相比降低了先兆子痫的风险。与GCC单倍型相比,AGT风险单倍型与较高的GPx活性相关。与对照组相比,子痫前期患者的铜水平明显升高,锌和硒水平明显降低。此外,与对照组相比,子痫前期患者的SOD明显降低,GPx活性明显升高。AA (rs7895833)、GG (rs7069102)和TT (rs2273773)三种危险基因型均显著降低锌水平和SOD活性,TT基因型(rs2273773)升高Cu水平。rs7069102多态性的存在与收缩压升高有关。我们首次指出SIRT1的三种多态性和AGT单倍型是子痫前期发展的危险因素。此外,SIRT1变异体和单倍型影响抗氧化酶及其辅助因子的水平,使妊娠结局复杂化。
{"title":"Variants and Haplotypes of SIRT1 (rs7895833, rs7069102, and rs2273773) are Associated with the Risk of Preeclampsia and Affect the Trace Elements and Antioxidant Enzymes Levels.","authors":"Fatemeh Khadir, Zohreh Rahimi, Asad Vaisi-Raygani, Ebrahim Shakiba, Mahdi Pouramir, Fariborz Bahrehmand","doi":"10.1007/s10528-023-10548-w","DOIUrl":"10.1007/s10528-023-10548-w","url":null,"abstract":"<p><p>Preeclampsia is the most common and serious complication of pregnancy. Variants of Sirtuin-1 (SIRT1) as a key player in the regulation of oxidant/antioxidant signaling pathways might be involved in the pathogenesis of preeclampsia. In the present case-control study 300 women with and without preeclampsia were studied for SIRT1 variants (rs7895833, rs7069102, and rs2273773) and haplotypes. Also, the relationship of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and Zn, Cu, and Se levels to the polymorphisms were investigated. The SIRT1 rs7895833 A > G, rs7069102 C > G, and the rs2273773 C > T polymorphisms were associated with the risk of preeclampsia. We found the haplotypes G (rs7895833) C (rs7069102) C (rs2273773), GCC, and ACC compared to the AGT decreased the risk of preeclampsia. The risk haplotype of AGT was associated with higher GPx activity compared to the GCC haplotype. A significantly higher level of Cu and lower levels of Zn and Se in patients with preeclampsia compared to controls were detected. Also, a significantly lower SOD and higher GPx activity in preeclamptic patients compared to controls were found. The three risk genotypes of AA (rs7895833), GG (rs7069102), and TT (rs2273773) significantly decreased the Zn level and SOD activity, and the TT genotype (rs2273773) increased the Cu level in all studied women. The presence of rs7069102 polymorphism was associated with enhanced systolic blood pressure. For the first time, we indicated three SIRT1 polymorphisms and the AGT haplotype are risk factors for preeclampsia development. Also, SIRT1 variants and haplotypes affect the levels of antioxidant enzymes and their cofactors, complicating the pregnancy outcome.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keloid is a kind of proliferative scar with continuous growth, no restriction and easy recurrence, which cannot be cured and bring serious physical injury and psychological burden to patients. The main reason is that the pathological mechanism is not clear. Therefore, this project is expected to reveal the immune microenvironment-related genes and their functions in keloid progression, and provide effective targets for the treatment of keloid. Firstly, 8 kinds of immune infiltrating cells and 19 potential characteristic genes were identified by immune infiltration analysis, ssGSEA, LASSO regression (glmnet algorithm and lars algorithm) and WGCNA, indicating that keloid was closely related to the changes of immune microenvironment. Then, 4 pathological biomarkers of keloid (MAPK1, PTPRC, STAT3 and IL1R1) were identified by differentially analysis, univariate analysis, LASSO regression (lars algorithm), support vector machine recursive feature elimination (SVM-REF) algorithm, multivariate logical regression analysis and six machine learning algorithms. Based on the 4 feature genes, the risk prediction model and nomogram were constructed. Calibration curve and ROC analysis (AUC = 0.930) showed that the model had reliable clinical value. Subsequently, consistent cluster analysis was used to find that there were 2 immune microenvironment subsets in keloid patients, of which subgroup II was immune subgroup. Multiple independent datasets and RT-qPCR showed that the expression trend of the 4 genes was consistent with the analysis. Cell gain-loss experiment confirmed that 4 genes regulated the proliferation and migration of keloid cells. The above data shows that MAPK1, PTPRC, STAT3 and IL1R1 may be personalized therapeutic targets for keloid patients.
{"title":"Identification and Analysis of Immune Microenvironment-Related Genes for Keloid Risk Prediction and Their Effects on Keloid Proliferation and Migration.","authors":"Yongyan Pei, Yikai Wu, Mengqi Zhang, Xuemin Su, Hua Cao, Jiaji Zhao","doi":"10.1007/s10528-023-10598-0","DOIUrl":"10.1007/s10528-023-10598-0","url":null,"abstract":"<p><p>Keloid is a kind of proliferative scar with continuous growth, no restriction and easy recurrence, which cannot be cured and bring serious physical injury and psychological burden to patients. The main reason is that the pathological mechanism is not clear. Therefore, this project is expected to reveal the immune microenvironment-related genes and their functions in keloid progression, and provide effective targets for the treatment of keloid. Firstly, 8 kinds of immune infiltrating cells and 19 potential characteristic genes were identified by immune infiltration analysis, ssGSEA, LASSO regression (glmnet algorithm and lars algorithm) and WGCNA, indicating that keloid was closely related to the changes of immune microenvironment. Then, 4 pathological biomarkers of keloid (MAPK1, PTPRC, STAT3 and IL1R1) were identified by differentially analysis, univariate analysis, LASSO regression (lars algorithm), support vector machine recursive feature elimination (SVM-REF) algorithm, multivariate logical regression analysis and six machine learning algorithms. Based on the 4 feature genes, the risk prediction model and nomogram were constructed. Calibration curve and ROC analysis (AUC = 0.930) showed that the model had reliable clinical value. Subsequently, consistent cluster analysis was used to find that there were 2 immune microenvironment subsets in keloid patients, of which subgroup II was immune subgroup. Multiple independent datasets and RT-qPCR showed that the expression trend of the 4 genes was consistent with the analysis. Cell gain-loss experiment confirmed that 4 genes regulated the proliferation and migration of keloid cells. The above data shows that MAPK1, PTPRC, STAT3 and IL1R1 may be personalized therapeutic targets for keloid patients.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138795237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-11-24DOI: 10.1007/s10528-023-10577-5
Soumaya Menadi, Burak Kucuk, Ercan Cacan
Pancreatic cancer (PC) is one of the world's most aggressive and deadly cancers, owing to non-specific early clinical symptoms, late-stage diagnosis, and poor survival. Therefore, it is critical to identify specific biomarkers for its early diagnosis. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein that has been reported to be upregulated in several cancer types, making it an emerging biomarker and potential cancer therapeutic target. However, the mechanism underlying the regulation of ANXA2 overexpression is still unclear. It is well established that genetic and epigenetic alterations may lead to widespread dysregulation of gene expression. Hence, in this study, we focused on exploring the regulatory mechanism of ANXA2 by investigating the transcriptional profile, methylation pattern, somatic mutation, and prognostic value of ANXA2 in PC using several bioinformatics databases. Our results revealed that the expression levels of ANXA2 were remarkably increased in PC tissues comparing to normal tissues. Furthermore, the high expression of ANXA2 was significantly related to the poor prognosis of PC patients. More importantly, we demonstrated for the first time that the ANXA2 promoter is hypomethylated in PC tissues compared to normal tissues which may result in ANXA2 overexpression in PC. However, more experimental research is required to corroborate our findings.
{"title":"Promoter Hypomethylation Upregulates ANXA2 Expression in Pancreatic Cancer and is Associated with Poor Prognosis.","authors":"Soumaya Menadi, Burak Kucuk, Ercan Cacan","doi":"10.1007/s10528-023-10577-5","DOIUrl":"10.1007/s10528-023-10577-5","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is one of the world's most aggressive and deadly cancers, owing to non-specific early clinical symptoms, late-stage diagnosis, and poor survival. Therefore, it is critical to identify specific biomarkers for its early diagnosis. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein that has been reported to be upregulated in several cancer types, making it an emerging biomarker and potential cancer therapeutic target. However, the mechanism underlying the regulation of ANXA2 overexpression is still unclear. It is well established that genetic and epigenetic alterations may lead to widespread dysregulation of gene expression. Hence, in this study, we focused on exploring the regulatory mechanism of ANXA2 by investigating the transcriptional profile, methylation pattern, somatic mutation, and prognostic value of ANXA2 in PC using several bioinformatics databases. Our results revealed that the expression levels of ANXA2 were remarkably increased in PC tissues comparing to normal tissues. Furthermore, the high expression of ANXA2 was significantly related to the poor prognosis of PC patients. More importantly, we demonstrated for the first time that the ANXA2 promoter is hypomethylated in PC tissues compared to normal tissues which may result in ANXA2 overexpression in PC. However, more experimental research is required to corroborate our findings.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138432996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}