Zi-Qian Liang, Wei Zhang, Da-Tong Zeng, Jun-Hong Chen, Jia-Yuan Luo, Lin Shi, Kang-Lai Wei, Gang Chen
{"title":"Upregulation of hsa-miR-141-3p promotes uterine cervical carcinoma progression via targeting dual-specificity protein phosphatase 1","authors":"Zi-Qian Liang, Wei Zhang, Da-Tong Zeng, Jun-Hong Chen, Jia-Yuan Luo, Lin Shi, Kang-Lai Wei, Gang Chen","doi":"10.1007/s10142-024-01413-z","DOIUrl":"10.1007/s10142-024-01413-z","url":null,"abstract":"<div><p>We aimed to explore the aberrant expression status of hsa-miR-141-3p and dual-specificity protein phosphatase 1 (DUSP1) and their relative mechanisms in uterine cervical carcinoma (UCC).Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was conducted to detect the expression of hsa-miR-141-3p. Immunohistochemical (IHC) staining was performed to examine the expression of DUSP1 in UCC. Gene chips and RNA-seq datasets were also obtained to assess the expression level. Integrated standardized mean difference (SMD) was calculated to evaluate the expression status of hsa-miR-141-3p in UCC tissues comprehensively. DUSP1-overexpression and hsa-miR-141-3p-inhibition HeLa cells were established, and CCK-8, transwell, wound healing, cell cycle, and apoptosis assays were implemented. The targets of hsa-miR-141-3p were obtained with online tools, and the combination of hsa-miR-141-3p and DUSP1 was validated via dual-luciferase reporter assay. Single-cell RNA-seq data were analyzed to explore hsa-miR-141-3p and DUSP1 in different cells. An integrated SMD of 1.41 (95% CI[0.45, 2.38], <i>p</i> = 0.0041) with 558 samples revealed the overexpression of hsa-miR-141-3p in UCC tissues. And the pooled SMD of -1.06 (95% CI[-1.45, -0.66], <i>p</i> < 0.0001) with 1,268 samples indicated the downregulation of DUSP1. Inhibition of hsa-miR-141-3p could upregulate DUSP1 expression and suppress invasiveness and metastasis of HeLa cells. Overexpression of DUSP1 could hamper proliferation, invasion, and migration and boost apoptosis and distribution of G1 phase. The dual-luciferase reporter assay validated the combination of hsa-miR-141-3p and DUSP1. Moreover, the targets of hsa-miR-141-3p were mainly enriched in the MAPK signaling pathway and activated in fibroblasts and endothelial cells. The current study illustrated the upregulation of hsa-miR-141-3p and the downregulation of DUSP1 in UCC tissues. Hsa-miR-141-3p could promote UCC progression by targeting DUSP1.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974821","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":"Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers","authors":"Wantao Wu, Gang Peng, Kaiyue Wang, Yijian Yang, Zhikun Liu, Gelei Xiao","doi":"10.1007/s10142-024-01416-w","DOIUrl":"10.1007/s10142-024-01416-w","url":null,"abstract":"<div><p>Protein disulfide isomerase A3 (PDIA3) is an endoplasmic reticulum (ER) protein. It has different functions including glycoprotein folding in the ER. The unfavorable prognosis of cancer patients was related to the abnormal PDIA3 expression level. However, it is unclear how PDIA3 correlates with the malignant characteristics of different tumors and its impact on tumor immunity. Pan-cancer data were downloaded from several databases for large-scale bioinformatics analysis. The immunological functions of PDIA3 were systematically explored at the single-cell sequencing level, including cell communication, cell metabolism, cell evolution and epigenetic modification. We performed immunofluorescence staining to visualize PDIA3 expression and infiltration of macrophages in pan-cancer samples. Further, we performed a loss-of-function assay of PDIA3 in vitro. The CCK8 assay, clone formation assay, and transwell assay were performed. M2 macrophages were co-cultured with different cell lines before the transwell assay was performed. The immunofluorescence staining of pan-cancer samples presented a higher expression of PDIA3 than those of the paired normal tissues. According to single-cell sequencing analysis, expression of PDIA3 was closely associated with cell communication, cell metabolism, cell evolution and epigenetic modification. The knockdown of PDIA3 in tumor cells inhibited cell proliferation and invasion, and restrained cocultured M2 macrophage migration. Furthermore, PDIA3 displayed predictive value in immunotherapy response in human cancer cohorts, indicating a potential therapeutic target. Our study showed that PDIA3 was associated with tumor malignant characteristics and could mediate the migration of M2 macrophages in various tumor types. PDIA3 could be a promising target to achieve tumor control and improve the immune response on a pan-cancer scale.</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 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974820","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":"PTBP1-mediated repression of neuron-specific CDC42 splicing constitutes a genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype glioblastoma","authors":"Junjie Yang, Jing Feng, Jing Lv, Xiaojing Chu, Yanfei Wei, Yunqiu Zhang, Jiuyi Li, Yingyu Sun, Guanzhang Li, Tao Jiang, Jinyan Huang, Xiaolong Fan","doi":"10.1007/s10142-024-01412-0","DOIUrl":"10.1007/s10142-024-01412-0","url":null,"abstract":"<div><p>Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform. Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. <i>PTBP1</i> is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905502","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}
Min Kong, Zhiheng Chen, Zhiqiang Lin, Ping Yin, Qin Zhao
{"title":"SIGMAR1 targets AMPK/ULK1 pathway to inhibit SH-SY5Y cell apoptosis by regulating endoplasmic reticulum stress and autophagy","authors":"Min Kong, Zhiheng Chen, Zhiqiang Lin, Ping Yin, Qin Zhao","doi":"10.1007/s10142-024-01414-y","DOIUrl":"10.1007/s10142-024-01414-y","url":null,"abstract":"<div><p>Distal hereditary motor neuropathy (dHMN) is a progressive neurological disease characterized by distal limb muscle weakness and amyotrophy. Sigma 1 receptor (σ1R), a gene product of SIGMAR1, mutations have been reported to induce dHMN, but its mechanism remains unknown. This study aims to explore the effect of C238T and 31_50del mutations in σ1R on neuronal SH-SY5Y cell functions. The SH-SY5Y cells that overexpressed σ1R, C238T mutant σ1R (σ1R<sup>C238T</sup>) or 31_50del mutant σ1R (σ1R<sup>31_50del</sup>) were constructed by pEGFPN1 vectors. We used Western blot (WB) and immunofluorescence (IF) staining to detect the expression of σ1R and green fluorescent proteins (GFP). Then, we evaluated the impact of σ1R mutation on apoptosis, autophagy, endoplasmic reticulum stress, and the involvement of the unfolded protein response (UPR) pathway in SH-SY5Y cells. We found that σ1R<sup>C238T</sup> and σ1R<sup>31_50del</sup> downregulated σ1R and promoted the apoptosis of SH-SY5Y cells. σ1R<sup>C238T</sup> and σ1R<sup>31_50del</sup> increased p-PERK, p-eIF2α, p-JNK, BIP, ATF4, CHOP, ATF6, XBP1, Caspase3, Caspase12 expressions and Ca<sup>2+</sup> concentration, whereas decreased ATP content in SH-SY5Y cells. Besides, the expressions of LC3B, Lamp1, ATG7, Beclin-1 and phosphorylation of AMPK and ULK1 were increased, while the p62 level decreased after C238T or 31_50del mutation of σ1R. Additionally, AMPK knockdown abolished the apoptosis mediated by σ1R<sup>C238T</sup> or σ1R<sup>31_50del</sup> in SH-SY5Y cells. Our results indicated that C238T or 31_50del mutation in σ1R promoted motor neuron apoptosis through the AMPK/ULK1 pathway in dHMN. This study shed light on a better understanding of the neurons pathological mechanisms mediated by σ1R C238T and σ1R 31-50del in dHMN.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896390","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}
Akshay Pramod Ware, Kapaettu Satyamoorthy, Bobby Paul
{"title":"CmirC update 2024: a multi-omics database for clustered miRNAs","authors":"Akshay Pramod Ware, Kapaettu Satyamoorthy, Bobby Paul","doi":"10.1007/s10142-024-01410-2","DOIUrl":"10.1007/s10142-024-01410-2","url":null,"abstract":"<div><p>Clustered miRNAs consist of two or more miRNAs transcribed together and may coordinately regulate gene expression. Differential expression of clustered miRNAs is found to be controlled by crosstalk of genetic or epigenetic mechanisms. It has been demonstrated that clustered miRNA expression patterns greatly impact cancer cell progression. With the <i>CmirC</i> initiative, we initially developed a comprehensive database to identify copy number variation (CNV) driven clustered miRNAs in cancer. Now, we extended the analysis and identified three miRNAs, mir-96, mir-183, and mir-21, were found to be significantly upregulated in 17 cancer types. Further, <i>CmirC</i> is now upgraded to determine the impact of changes in the DNA methylation status at clustered miRNAs by utilizing The Cancer Genomic Atlas (TCGA) cancer datasets. We examined specific methylation datasets from 9,639 samples, pinpointing 215,435 methylation sites and 27,949 CpG islands with miRNA cluster information. The integrated analysis identified 34 clusters exhibiting differentially methylated CpG sites across 14 cancer types. Furthermore, we determined that CpG islands in the promoter region of 20 miRNA clusters could play a regulatory role. Along with ensuring a straightforward and convenient user experience, <i>CmirC</i> has been updated with improved data browsing and analysis functionalities, as well as enabled hyperlinks to literature and miR-cancer databases. The enhanced version of <i>CmirC</i> is anticipated to play an important role in providing information on the regulation of clustered miRNA expression, and their targeted oncogenes and tumor suppressors. The newly updated version of <i>CmirC</i> is available at https://slsdb.manipal.edu/cmirclust/.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858710","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}
Muhammad Waqas Choudry, Rabia Riaz, Pashma Nawaz, Maria Ashraf, Bushra Ijaz, Allah Bakhsh
{"title":"CRISPR-Cas9 mediated understanding of plants’ abiotic stress-responsive genes to combat changing climatic patterns","authors":"Muhammad Waqas Choudry, Rabia Riaz, Pashma Nawaz, Maria Ashraf, Bushra Ijaz, Allah Bakhsh","doi":"10.1007/s10142-024-01405-z","DOIUrl":"10.1007/s10142-024-01405-z","url":null,"abstract":"<div><p>Multiple abiotic stresses like extreme temperatures, water shortage, flooding, salinity, and exposure to heavy metals are confronted by crop plants with changing climatic patterns. Prolonged exposure to these adverse environmental conditions leads to stunted plant growth and development with significant yield loss in crops. CRISPR-Cas9 genome editing tool is being frequently employed to understand abiotic stress-responsive genes. Noteworthy improvements in CRISPR-Cas technology have been made over the years, including upgradation of Cas proteins fidelity and efficiency, optimization of transformation protocols for different crop species, base and prime editing, multiplex gene-targeting, transgene-free editing, and graft-based heritable CRISPR-Cas9 approaches. These developments helped to improve the knowledge of abiotic stress tolerance in crops that could potentially be utilized to develop knock-out varieties and over-expressed lines to tackle the adverse effects of altered climatic patterns. This review summarizes the mechanistic understanding of heat, drought, salinity, and metal stress-responsive genes characterized so far using CRISPR-Cas9 and provides data on potential candidate genes that can be exploited by modern-day biotechnological tools to develop transgene-free genome-edited crops with better climate adaptability. Furthermore, the importance of early-maturing crop varieties to withstand abiotic stresses is also discussed in this review.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791619","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}
Weijian Xiong, Jing Tang, Hangxing Yu, Yan Luo, Minghuan Yu, Ying Li
{"title":"Emodin inhibits M1 macrophage activation that related to acute and chronic kidney injury through EGFR/MAPK pathway","authors":"Weijian Xiong, Jing Tang, Hangxing Yu, Yan Luo, Minghuan Yu, Ying Li","doi":"10.1007/s10142-024-01407-x","DOIUrl":"10.1007/s10142-024-01407-x","url":null,"abstract":"<div><h3>Background</h3><p>Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages.</p><h3>Methods</h3><p>Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1β, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD.</p><h3>Results</h3><p>There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1β and TNF-α (<i>p</i> < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (<i>p</i> < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway.</p><h3>Conclusion</h3><p>Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791620","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}
Flávia Maria Campos de Abreu, Deborah Almeida de Oliveira, Sabrina Simplício de Araujo Romero Ferrari, Karla Helena Coelho Vilaça e Silva, Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida
{"title":"Exploring circular RNAs as biomarkers for Parkinson’s disease and their expression changes after aerobic exercise rehabilitation","authors":"Flávia Maria Campos de Abreu, Deborah Almeida de Oliveira, Sabrina Simplício de Araujo Romero Ferrari, Karla Helena Coelho Vilaça e Silva, Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida","doi":"10.1007/s10142-024-01409-9","DOIUrl":"10.1007/s10142-024-01409-9","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are circularized single-stranded ribonucleic acids that interacts with DNA, RNA, and proteins to play critical roles in cell biology. CircRNAs regulate microRNA content, gene expression, and may code for specific peptides. Indeed, circRNAs are differentially expressed in neurodegenerative disorders like Parkinson’s disease (PD), playing a potential role in the mechanisms of brain pathology. The RNA molecules with aberrant expression in the brain can cross the blood–brain barrier and reach the bloodstream, which enable their use as non-invasive PD disease biomarker. Promising targets with valuable discriminatory ability in combined circRNA signatures include MAPK9_circ_0001566, SLAIN1_circ_0000497, SLAIN2_circ_0126525, PSEN1_circ_0003848, circ_0004381, and circ_0017204. On the other hand, regular exercises are effective therapy for mitigating PD symptoms, promoting neuroprotective effects with epigenetic modulation. Aerobic exercises slow symptom progression in PD by improving motor control, ameliorating higher functions, and enhancing brain activity and neuropathology. These improvements are accompanied by changes circRNA expression, including hsa_circ_0001535 (circFAM13B) and hsa_circ_0000437 (circCORO1C). The sensitivity of current methods for detecting circulating circRNAs is considered a limitation. While amplification kits already exist for low-abundant microRNAs, similar kits are needed for circRNAs. Alternatively, the use of digital PCR can help overcome this constraint. The current review examines the potential use of circRNAs as non-invasive biomarkers of PD and to assess the effects of rehabilitation. Although circRNAs hold promise as targets for PD diagnosis and therapeutics, further validation is needed before their clinical implementation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787005","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}
Tereza Cristina L. Castellane, Camila C. Fernandes, Daniel G. Pinheiro, Manoel Victor Franco Lemos, Alessandro M. Varani
{"title":"Exploratory comparative transcriptomic analysis reveals potential gene targets associated with Cry1A.105 and Cry2Ab2 resistance in fall armyworm (Spodoptera frugiperda)","authors":"Tereza Cristina L. Castellane, Camila C. Fernandes, Daniel G. Pinheiro, Manoel Victor Franco Lemos, Alessandro M. Varani","doi":"10.1007/s10142-024-01408-w","DOIUrl":"10.1007/s10142-024-01408-w","url":null,"abstract":"<div><p>Genetically modified (GM) crops, expressing <i>Bacillus thuringiensis</i> (Bt) insecticidal toxins, have substantially transformed agriculture. Despite rapid adoption, their environmental and economic benefits face scrutiny due to unsustainable agricultural practices and the emergence of resistant pests like <i>Spodoptera frugiperda</i>, known as the fall armyworm (FAW). FAW’s adaptation to Bt technology in corn and cotton compromises the long-term efficacy of Bt crops. To advance the understanding of the genetic foundations of resistance mechanisms, we conducted an exploratory comparative transcriptomic analysis of two divergent FAW populations. One population exhibited practical resistance to the Bt insecticidal proteins Cry1A.105 and Cry2Ab2, expressed in the genetically engineered MON-89Ø34 − 3 maize, while the other population remained susceptible to these proteins. Differential expression analysis supported that Cry1A.105 and Cry2Ab2 significantly affect the FAW physiology. A total of 247 and 254 differentially expressed genes were identified in the Cry-resistant and susceptible populations, respectively. By integrating our findings with established literature and databases, we underscored 53 gene targets potentially involved in FAW’s resistance to Cry1A.105 and Cry2Ab2. In particular, we considered and discussed the potential roles of the differentially expressed genes encoding ABC transporters, G protein-coupled receptors, the P450 enzymatic system, and other Bt-related detoxification genes. Based on these findings, we emphasize the importance of exploratory transcriptomic analyses to uncover potential gene targets involved with Bt insecticidal proteins resistance, and to support the advantages of GM crops in the face of emerging challenges.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747079","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}
Shailendra Pratap Singh, Dileep Kumar Yadav, Mohammad Kazem Chamran, Darshika G. Perera
{"title":"Intelligent mutation based evolutionary optimization algorithm for genomics and precision medicine","authors":"Shailendra Pratap Singh, Dileep Kumar Yadav, Mohammad Kazem Chamran, Darshika G. Perera","doi":"10.1007/s10142-024-01401-3","DOIUrl":"10.1007/s10142-024-01401-3","url":null,"abstract":"<div><p>In this paper, genomics and precision medicine have witnessed remarkable progress with the advent of high-throughput sequencing technologies and advances in data analytics. However, because of the data’s great dimensionality and complexity, the processing and interpretation of large-scale genomic data present major challenges. In order to overcome these difficulties, this research suggests a novel Intelligent Mutation-Based Evolutionary Optimization Algorithm (IMBOA) created particularly for applications in genomics and precision medicine. In the proposed IMBOA, the mutation operator is guided by genome-based information, allowing for the introduction of variants in candidate solutions that are consistent with known biological processes. The algorithm’s combination of Differential Evolution with this intelligent mutation mechanism enables effective exploration and exploitation of the solution space. Applying a domain-specific fitness function, the system evaluates potential solutions for each generation based on genomic correctness and fitness. The fitness function directs the search toward ideal solutions that achieve the problem’s objectives, while the genome accuracy measure assures that the solutions have physiologically relevant genomic properties. This work demonstrates extensive tests on diverse genomics datasets, including genotype-phenotype association studies and predictive modeling tasks in precision medicine, to verify the accuracy of the proposed approach. The results demonstrate that, in terms of precision, convergence rate, mean error, standard deviation, prediction, and fitness cost of physiologically important genomic biomarkers, the IMBOA consistently outperforms other cutting-edge optimization methods.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733153","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}