Tohada M. AL-Noshokaty, Rehab Abdelhamid, Tasnim Reda, Ayat Alaaeldien, Nourhan Abdellatif, Abdallah Mansour, David Gendi, Nourhan M. Abdelmaksoud, Shereen Saeid Elshaer, Ahmed S. Doghish, Mohamed Hossam Sobhy, Osama A. Mohammed, Ahmed I. Abulsoud
{"title":"Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions","authors":"Tohada M. AL-Noshokaty, Rehab Abdelhamid, Tasnim Reda, Ayat Alaaeldien, Nourhan Abdellatif, Abdallah Mansour, David Gendi, Nourhan M. Abdelmaksoud, Shereen Saeid Elshaer, Ahmed S. Doghish, Mohamed Hossam Sobhy, Osama A. Mohammed, Ahmed I. Abulsoud","doi":"10.1007/s10142-024-01476-y","DOIUrl":"10.1007/s10142-024-01476-y","url":null,"abstract":"<div><p>Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595413","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}
{"title":"Circular RNA circ_0022707 impedes the progression of preeclampsia via the miR-3135b/GHR/PI3K/Akt axis","authors":"Huijing Shao, Rui Guan, Zixi Chen, Ruijiao Kong, Caihong Zhang, Hang Gu","doi":"10.1007/s10142-024-01490-0","DOIUrl":"10.1007/s10142-024-01490-0","url":null,"abstract":"<div><p>Preeclampsia (PE) is a severe pregnancy complication linked to maternal and fetal health, yet its underlying causes and pathogenesis remain elusive. Circular RNA (circRNA), a form of non-coding RNA, is implicated in the progression of PE; nevertheless, the specific mechanism is not fully elucidated. This study aimed to identify and validate circRNAs that are pivotal in the pathophysiology of PE. Firstly, we constructed a ceRNA network using datasets from the GEO database and identified circ_0022707 as our study target. Then, using qRT-PCR analysis, we validated that circ_0022707 was downregulated in preeclamptic placentas compared to those of normal pregnant women. In situ hybridization assays revealed that circ_0022707 existed in placental villous trophoblast cells. Additionally, Pearson correlation analysis revealed a negative relationship between the expression of circ_0022707 and PE-related indicators (systolic and diastolic blood pressure, along with 24-h proteinuria levels). Furthermore, gain-of-function experiments confirmed that circ_0022707 could promote trophoblast cell proliferation and cell cycle progression while suppressing apoptosis. In vivo experiments using a preeclampsia-like mouse model also demonstrated that circ_0022707 administration could mitigate preeclampsia-like symptoms. Mechanistically, we confirmed that circ_0022707 functions through the miR-3135b/<i>GHR</i>/PI3K/Akt pathway in trophoblast cells. Overall, our study has provided insight into the important function of circ_002707 in the development of PE, enhancing our understanding of the disease's mechanism and proposing a viable therapeutic strategy for PE.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581576","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}
{"title":"Integration of CRISPR/Cas9 with multi-omics technologies to engineer secondary metabolite productions in medicinal plant: Challenges and Prospects","authors":"Anupriya Borah, Shailey Singh, Rituja Chattopadhyay, Jaspreet Kaur, Vinay Kumar Bari","doi":"10.1007/s10142-024-01486-w","DOIUrl":"10.1007/s10142-024-01486-w","url":null,"abstract":"<div><p>Plants acts as living chemical factories that may create a large variety of secondary metabolites, most of which are used in pharmaceutical products. The production of these secondary metabolites is often much lower. Moreover, the primary constraint after discovering potential metabolites is the capacity to manufacture sufficiently for use in industrial and therapeutic contexts. The development of omics technology has brought revolutionary discoveries in various scientific fields, including transcriptomics, metabolomics, and genome sequencing. The metabolic pathways leading to the utilization of new secondary metabolites in the pharmaceutical industry can be identified with the use of these technologies. Genome editing (GEd) is a versatile technology primarily used for site-directed DNA insertions, deletions, replacements, base editing, and activation/repression at the targeted locus. Utilizing GEd techniques such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR-associated protein 9), metabolic pathways engineered to synthesize bioactive metabolites optimally. This article will briefly discuss omics and CRISPR/Cas9-based methods to improve secondary metabolite production in medicinal plants.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574816","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}
A Ghane, PK Malhotra, GS Sanghera, SK Verma, NS Jamwal, L Kashyap, SH Wani
{"title":"CRISPR/Cas technology: fueling the future of Biofuel production with sugarcane","authors":"A Ghane, PK Malhotra, GS Sanghera, SK Verma, NS Jamwal, L Kashyap, SH Wani","doi":"10.1007/s10142-024-01487-9","DOIUrl":"10.1007/s10142-024-01487-9","url":null,"abstract":"<div><p>The objective of present review is to provide a scientific overview of sugarcane as a potential feedstock for biofuel and use of genome editing approach for improvement of industrial and agronomical traits in sugarcane. Sugarcane, a perennial tropical grass with a high biomass index, is a promising feedstock for bioethanol production, and its bagasse, rich in lignocellulosic material, serves as an ideal feedstock for producing second-generation bioethanol. To improve the conversion of sugarcane biomass into biofuels, developing varieties with improved biomass degradability and high biomass and sucrose content is essential. The complex genome architecture and earlier lack of sequence data hindered biotechnological advancements in sugarcane, but recent genome sequence updates offer new opportunities for sugarcane improvement. The first genetically modified sugarcane was developed in 1992 by Bower and Birch using microprojectile bombardment of embryogenic callus. Since then, transgenic techniques have rapidly evolved, leading to the advancement of genome editing technologies. Application of genome editing tools particularly CRISPR/Cas system has been successfully used in sugarcane for editing. Recently, multiple alleles of the magnesium chelatase and acetolactate synthase genes in sugarcane have been successfully edited through multiplexing. Additionally, CRISPR-edited sugarcane varieties with modified cell wall components and increased sucrose content for enhanced bioethanol production have been developed. At the end, the future of CRISPR-edited crops will depend on how well regulatory frameworks adapt to the rapidly evolving technology.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567163","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}
{"title":"Breast cancer genomic analyses reveal genes, mutations, and signaling networks","authors":"Gowrang Kasaba Manjunath, Srihari Sharma, Disha Nashier, Shruthi Vasanthaiah, Spriha Jha, Saloni Bage, Tamoghna Mitra, Pankaj Goyal, Muniasamy Neerathilingam, Abhishek Kumar","doi":"10.1007/s10142-024-01484-y","DOIUrl":"10.1007/s10142-024-01484-y","url":null,"abstract":"<div><p>Breast cancer (BC) is the most commonly diagnosed cancer and the predominant cause of death in women. BC is a complex disorder, and the exploration of several types of BC omic data, highlighting genes, perturbations, signaling and cellular mechanisms, is needed. We collected mutational data from 9,555 BC samples using cBioPortal. We classified 1174 BC genes (mutated ≥ 40 samples) into five tiers (BCtier_I-V) and subjected them to pathway and protein‒protein network analyses using EnrichR and STRING 11, respectively. BCtier_I possesses 12 BC genes with mutational frequencies > 5%, with only 5 genes possessing > 10% frequencies, namely, PIK3CA (35.7%), TP53 (34.3%), GATA3 (11.5%), CDH1 (11.4%) and MUC16 (11%), and the next seven BC genes are KMT2C (8.8%), TTN (8%), MAP3K1 (8%), SYNE1 (7.2%), AHNAK2 (7%), USH2A (5.5%), and RYR2 (5.4%). Our pathway analyses revealed that the five top BC pathways were the PI3K-AKT, TP53, NOTCH, HIPPO, and RAS pathways. We found that BC panels share only seven genes. These findings show that BC arises from genetic disruptions evident in BC signaling and protein networks.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574796","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}
Fuchuang Qin, Hang Tan, Yang Yang, Liping Xu, Xiaofeng Yang
{"title":"Upregulation of Cullin1 neddylation promotes glycolysis and M1 polarization of macrophage via NF-κB p65 pathway in sepsis","authors":"Fuchuang Qin, Hang Tan, Yang Yang, Liping Xu, Xiaofeng Yang","doi":"10.1007/s10142-024-01483-z","DOIUrl":"10.1007/s10142-024-01483-z","url":null,"abstract":"<div><p>This study aimed to explore the underlying mechanism of neddylation in macrophage polarization during sepsis. A mouse model of sepsis was established by cecal ligation and puncture (CLP). ELISA and Flow cytometry were performed to analyze the generation of pro-inflammatory factors and M1/M2 macrophage polarization, respectively. Western blotting was applied to detect NEDD8-mediated neddylation and glycolysis-related proteins. ECAR method was used to analyze the glycolysis level. HE staining was applied to detect the lung injury. The bacterial load in peritoneal cavity and peripheral blood was determined by counting the colony-forming units. The results showed the upregulated neddylation, M1 polarization and glycolysis of macrophage in patients with sepsis and CLP-challenged mice. NEDD8-mediated Cullin1 neddylation promoted M1 polarization and glycolysis to accelerate inflammation via NF-κB p65 pathway in E.coli-treated Raw264.7 cells. MLN4924 treatment alleviated sepsis by inhibiting neddylation to prevent M1 polarization in CLP-challenged mice. In summary, this study demonstrated that upregulation of NEDD8-mediated Cullin1 neddylation promotes glycolysis and M1 polarization of macrophage via NF-κB p65 pathway, accelerating inflammation in sepsis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540510","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}
{"title":"GWAS for identification of genomic regions and candidate genes in vegetable crops","authors":"Swagata Nandi, Kishor Varotariya, Sohamkumar Luhana, Amitkumar D. Kyada, Ankita Saha, Nabanita Roy, Neha Sharma, Dharavath Rambabu","doi":"10.1007/s10142-024-01477-x","DOIUrl":"10.1007/s10142-024-01477-x","url":null,"abstract":"<div><p>Genome-wide association Studies (GWAS), initially developed for human genetics, have been highly effective in plant research, particularly for vegetable crops. GWAS is a robust tool for identifying genes associated with key traits such as yield, nutritional value, disease resistance, adaptability, and bioactive compound biosynthesis. Unlike traditional methods, GWAS does not require prior biological knowledge and can accurately pinpoint loci, minimizing false positives. The process involves developing a diverse panel, rigorous phenotyping and genotyping, and sophisticated statistical analysis using various models and software tools. By scanning the entire genome, GWAS identifies specific loci or single nucleotide polymorphisms (SNPs) linked to target traits. When a causal SNP variant is not directly genotyped, GWAS identifies SNPs in linkage disequilibrium (LD) with the causal variant, mapping the genetic interval. The method begins with careful panel selection, phenotyping, and genotyping, controlling for environmental effects and utilizing Best Linear Unbiased Prediction (BLUP). High-correlation, high-heritability traits are prioritized. Various genotyping methods address confounders like population structure and kinship. Bonferroni correction (BC) prevents false positives, and significant associations are shown in Manhattan plots. Candidate genes are identified through LD analysis and fine mapping, followed by functional validation. GWAS offers critical insights for enhancing vegetable crop breeding efficiency and precision, driving breakthroughs through advanced methods.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524518","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}
Siddharth Panda, Annamalai Anandan, K. Mohamed Shafi, Mahantesha B. N. Naika, R. Sowdhamini, G. Vanishree, Sutapa Sarkar, Anthony J. Travis, Gareth J. Norton, Adam H. Price
{"title":"Genome-wide association study reveals effect of nsSNPs on candidate genes in rice during iron deficiency","authors":"Siddharth Panda, Annamalai Anandan, K. Mohamed Shafi, Mahantesha B. N. Naika, R. Sowdhamini, G. Vanishree, Sutapa Sarkar, Anthony J. Travis, Gareth J. Norton, Adam H. Price","doi":"10.1007/s10142-024-01478-w","DOIUrl":"10.1007/s10142-024-01478-w","url":null,"abstract":"<div><p>Resource-poor areas with moisture deficit lands following aerobic and direct seeded rice (DSR) methods of cultivation face severe problems of iron deficiency. In this study, Bengal and Assam Aus rice panel was phenotyped at the seedling stage using an iron-deprived hydroponic medium for various shoot and root traits. A novel iron deficiency scoring scale was used to classify the tolerance reaction and could range anywhere between 0 and 9, indicating the most tolerant and susceptible, respectively. The GWAS results identified four putative candidate genes; <i>OsFLA</i> for number of leaves and shoot length, <i>OsBIDK1</i> for root traits; average diameter, volume, biomass, projected area, and surface area, <i>OsHPL3</i> for chlorophyll index of the third leaf and <i>AKR2B</i> (<i>XBOS252</i>) was for Fe score, (which was earlier reported in relation to <i>Xa21</i>). The nsSNP (nsSNPs) variations in these gene sequences were used to group the panel and identify superior haplotypes and donors. BR16 was identified as a superior donor, with higher chlorophyll index and shoot length than RA23, also higher values for root traits like root average diameter, root volume, root projected area and root surface area followed by Shete Bhado. The impact of identified nsSNPs on protein structure and stability was investigated. The conserved domains detected in the mutated proteins of the superior haplotypes are very informative, highlighting that natural selection favors abiotic stress tolerant variants in resource poor areas. Thus, justifying our choice of <i>Aus</i> landraces for association mapping of Fe deficiency tolerant genes in rice.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492574","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}
{"title":"CRISPR/Cas9 mediated genome editing for crop improvement against Abiotic stresses: current trends and prospects","authors":"Mestawut Adane, Getachew Alamnie","doi":"10.1007/s10142-024-01480-2","DOIUrl":"10.1007/s10142-024-01480-2","url":null,"abstract":"<div><p>Abiotic stresses associated with climate change, such as heat, cold, salinity, and drought, represent a serious threat to crop health. To mitigate the risks posed by these environmental challenges, both transgenic technology and conventional breeding methods have been extensively utilized. However, these methods have faced numerous limitations. The development of synthetic nucleases as precise genetic tools allows for the targeted alteration of stress-responsive genes in crop improvement. The clustered regularly interspaced short palindromic repeats (CRISPR/Cas) genome-editing technique has transformed gene editing with its broad applicability, accessibility, adaptability, flexibility, and simplicity. Its application shows promise for the development of crop types that are more able to survive abiotic stress conditions. The present study presents recent scenario and application of CRISPR/Cas genome-editing technology in enhancing crop tolerance to a variety of abiotic stresses.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492572","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}
{"title":"ANPS: machine learning based server for identification of anti-nutritional proteins in plants","authors":"Sanchita Naha, Sarvjeet Kaur, Ramcharan Bhattacharya, Srinivasulu Cheemanapalli, Yuvaraj Iyyappan","doi":"10.1007/s10142-024-01474-0","DOIUrl":"10.1007/s10142-024-01474-0","url":null,"abstract":"<div><p>Anti-nutrient factors are inherently present in almost all major crops, which impede the absorption of crucial vitamins and minerals upon human consumption. The commonly found anti-nutrients in food crops are saponins, tannins, lectins, and phytates etc. Currently, there is a lack of computational server for identification of proteins that encode for anti-nutritional factors in plants. Consequently, this study represents a computational approach aimed at distinguishing between proteins encoding anti-nutritional factors and those providing essential nutrients. In this work, machine learning algorithms have been employed to identify plant specific anti-nutrient factor proteins from protein sequences by using compositional features. Achieving a five-fold cross-validation training performance of 94.34% AUC-ROC and 94.13% AUC-PR with extreme gradient boosting surpasses the performance of other methods such as support vector machine, random forest, and adaptive boosting. These results suggest the proposed approach is highly reliable in predicting plant-specific anti-nutritional factor proteins. The resulting prediction models have led to the development of an online server named ANPS, freely available at https://nipb-bi.icar.gov.in.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492571","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}