Genes & genomics最新文献

{"title":"MiR-122, miR-133a, and miR-206 as potential biomarkers for post-mortem interval estimation.","authors":"Eun Ju Lee, Mingyoung Jeong, Haneul Lee, Min-A Je, Kwangmin Park, Dong Geon Lee, Xianglan Xuan, Sunghyun Kim, Sunyoung Park, Jungho Kim","doi":"10.1007/s13258-024-01559-x","DOIUrl":"10.1007/s13258-024-01559-x","url":null,"abstract":"<p><strong>Backgroud: </strong>Accurate estimation of post-mortem interval (PMI) is crucial in forensic investigations. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that remain relatively stable within the cell nucleus despite post-mortem changes.</p><p><strong>Objective: </strong>We assessed three target genes (miR-122, miR-133a, and miR-206) for PMI estimation using 72 healthy adult male BALB/c mice exposed to two different temperatures (4 and 21℃) at nine different time points over 10 days.</p><p><strong>Methods: </strong>Initially, the stability of the two reference genes (RNU6B and 5 srRNA) was evaluated using gene stability analysis tools (Delta Ct, Best Keeper, and Genorm) to select the optimal reference gene. RNU6B was found to be the most stable endogenous control. Subsequently, the expression patterns of miR-122, miR-133a, and miR-206 were analyzed within a 10-day PMI period using the heart, skeletal muscle, liver, and brain tissues.</p><p><strong>Results: </strong>At 4℃, miR-122 levels significantly decreased on days 8 and 10 in all tissues, with only the liver showing significant changes at 21℃. MiR-133a decreased over time in the heart, muscles, and brain, showing a dramatic decrease on days 8 and 10 in the heart and muscles at both temperatures. Although miR-206 levels decreased over time in muscles and liver at 4 ℃, these increased in the brain at 21 ℃, with no expression changes in other organs.</p><p><strong>Conclusion: </strong>In summary, miR-122, miR-133a, and miR-206 are potential PMI markers in heart and skeletal muscle tissues.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106600","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":"Identification of an autophagy- and macropinocytosis-related prognostic signature for the prediction of prognosis and therapeutic response in gastric cancer.","authors":"Yuhua Shi, Aifeng Qiu, Hengfeng Cui, Heng Lv, Lei Zhou","doi":"10.1007/s13258-024-01557-z","DOIUrl":"10.1007/s13258-024-01557-z","url":null,"abstract":"<p><strong>Background: </strong>Traditional liquid biopsy markers show a low rate of positivity and accurate in gastric cancer. With the rapid advancement of sequencing technology, scientists have identified promising research avenues in this field. Autophagy and macropinocytosis utilize diverse pathways and mechanisms to supply resources and fuel for tumor growth. Nonetheless, their potential interplay introduces an untapped avenue for the discovery of novel tumor biomarkers.</p><p><strong>Objective: </strong>To develop an innovative prognostic signature based on autophagy- and micropinocytosis-related genes, with the aim to predict the outcome and therapeutic response of gastric cancer patients. Additionally, to validate the prognostic impact of this signature, and elucidate the role of representative molecules in gastric cancer.</p><p><strong>Methods: </strong>To construct and validate a prognostic signature for gastric cancer, bioinformatics methods such as COX regression, LASSO regression, survival analysis, ROC curve, and nomogram were utilized based on the sequencing and clinical data of gastric cancer patients retrieved from the TCGA and GEO databases. GSEA functional enrichment analyses were employed to predict the biological functions. Meanwhile, qRT-PCR and Western blot experiments were utilized to quantify the mRNA and protein expression levels. Furthermore, the EdU assay and colony formation assay were utilized to examine the cell proliferation ability while the Transwell assays were conducted to assess the migration and invasion abilities of gastric cancer cells.</p><p><strong>Results: </strong>Through consistency clustering and univariate COX analyses, potential prognostic genes involved in both autophagy and macropinocytosis were identified. Based on these genes, a 9-gene signature was constructed, which demonstrated high accuracy in predicting gastric cancer patients' survival period, immunotherapeutic response, and chemotherapy drug tolerance. Furthermore, qRT-PCR analyses of gastric cancer tissue samples showed that the representative genes of this signature were aberrantly overexpressed in gastric cancer, with MATN3, as the most notable molecule, exhibiting significant carcinogenic effects on cancer cells by actively regulating their proliferation, migration, and invasion abilities.</p><p><strong>Conclusion: </strong>Our newly created prognostic signature possesses significant potential as a biomarker for gastric cancer, while MATN3 is identified as an oncogenic factor in gastric cancer. This brings to light new perspectives, which can contribute to enhancing the diagnosis and treatment of gastric cancer.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987777","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":"Prognostic significance of HS2ST1 expression in patients with hepatocellular carcinoma.","authors":"Ting Ting Chung, Sang Kyum Kim, Seung Jin Lee","doi":"10.1007/s13258-024-01556-0","DOIUrl":"10.1007/s13258-024-01556-0","url":null,"abstract":"<p><strong>Background: </strong>Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) catalyzes the sulfation of glucuronic acid residues in heparan sulfate proteoglycans, enabling these proteoglycans to interact with numerous ligands within tumor microenvironments. However, the prognostic role of HS2ST1 expression in cancer remains unclear.</p><p><strong>Objective: </strong>This investigated HS2ST1 expression levels and their prognostic significance in various cancer types, demonstrated the prognostic value of HS2ST1 expression in hepatocellular carcinoma (HCC) patients, and identified molecular signatures associated with HS2ST1 expression.</p><p><strong>Methods: </strong>HS2ST1 expression and patient survival data from The Cancer Genome Atlas (TCGA) datasets were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) portal. We obtained gene expression and clinicopathological information on HCC patients from the TCGA and the Japan and France International Cancer Genome Consortium (ICGC) databases and performed survival analyses. We also examined relevant protein networks, differentially expressed genes, gene set enrichments, and tumor immune microenvironment features associated with HS2ST1 expression.</p><p><strong>Results: </strong>HS2ST1 exhibited higher expression in eight tumor types compared with normal tissues and was associated with poor prognoses in five tumors, including HCC. HS2ST1 status correlated with poor prognosis in two ICGC HCC cohorts. Elevated HS2ST1 expression in HCC tumors was associated with signaling pathways involved in cell cycle progression, protein secretion, and mTORC1 signaling. Moreover, HS2ST1 expression levels were inversely correlated with immune cell infiltration in the tumor microenvironment.</p><p><strong>Conclusion: </strong>Our study elucidates the prognostic significance of HS2ST1 expression in HCC patients and provides insights into the potential roles of HS2ST1 in signaling pathways and the tumor microenvironment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995644","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}

{"title":"A novel study on CXXC5: unraveling its regulatory mechanisms in hematopoietic stem cell biology through proteomics and gene editing.","authors":"Shanshan Liu, Yan Gao, Xianqi Feng, Yujie Xu, Minghui Hu, Hairong Fei, Hongying Zheng, Junxia Huang, Tianlan Li, Chunting Zhao, Lingjie Sun","doi":"10.1007/s13258-024-01540-8","DOIUrl":"10.1007/s13258-024-01540-8","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the role of CXXC5 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) within the bone marrow microenvironment, utilizing advanced methodologies such as single-cell RNA sequencing (scRNA-seq), CRISPR-Cas9, and proteomic analysis.</p><p><strong>Methods: </strong>We employed flow cytometry to isolate HSCs from bone marrow samples, followed by scRNA-seq analysis using the 10x Genomics platform to examine cell clustering and CXXC5 expression patterns. CRISPR-Cas9 and lentiviral vectors facilitated the knockout and overexpression of CXXC5 in HSCs. The impact on HSCs was assessed through qRT-PCR, Western blot, CCK-8, CFU, and LTC-IC assays, alongside flow cytometry to measure apoptosis and cell proportions. A mouse model was also used to evaluate the effects of CXXC5 manipulation on HSC engraftment and survival rates.</p><p><strong>Results: </strong>Our findings highlight the diversity of cell clustering and the significant role of CXXC5 in HSC regulation. Knockout experiments showed reduced proliferation and accelerated differentiation, whereas overexpression led to enhanced proliferation and delayed differentiation. Proteomic analysis identified key biological processes influenced by CXXC5, including cell proliferation, differentiation, and apoptosis. In vivo results demonstrated that CXXC5 silencing impaired HSC engraftment in a bone marrow transplantation model.</p><p><strong>Conclusion: </strong>CXXC5 is crucial for the regulation of HSC self-renewal and differentiation in the bone marrow microenvironment. Its manipulation presents a novel approach for enhancing HSC function and provides a potential therapeutic target for hematological diseases.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987776","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":"Kernel-based hierarchical structural component models for pathway analysis on survival phenotype.","authors":"Suhyun Hwangbo, Sungyoung Lee, Md Mozaffar Hosain, Taewan Goo, Seungyeoun Lee, Inyoung Kim, Taesung Park","doi":"10.1007/s13258-024-01569-9","DOIUrl":"https://doi.org/10.1007/s13258-024-01569-9","url":null,"abstract":"<p><strong>Background: </strong>High-throughput sequencing, particularly RNA-sequencing (RNA-seq), has advanced differential gene expression analysis, revealing pathways involved in various biological conditions. Traditional pathway-based methods generally consider pathways independently, overlooking the correlations among them and ignoring quite a few overlapping biomarkers between pathways. In addition, most pathway-based approaches assume that biomarkers have linear effects on the phenotype of interest.</p><p><strong>Objective: </strong>This study aims to develop the HisCoM-KernelS model to identify survival phenotype-related pathways by accommodating complex, nonlinear relationships between genes and survival outcomes, while accounting for inter-pathway correlations.</p><p><strong>Methods: </strong>We applied HisCoM-KernelS model to the TCGA pancreatic ductal adenocarcinoma (PDAC) RNA-seq dataset, comprising 4,498 protein-coding genes mapped to 186 KEGG pathways from 148 PDAC samples. Kernel machine regression was used to model pathway effects on survival outcomes, incorporating hierarchical gene-pathway structures. Model parameters were estimated using the alternating least squares algorithm, and the significance of pathways was assessed through a permutation test.</p><p><strong>Results: </strong>HisCoM-KernelS identified several pathways significantly associated with pancreatic cancer survival, including those corroborated by previous studies. HisCoM-KernelS, especially with the Gaussian kernel, showed a better balance of detection rate and number of significant pathways compared to four other existing pathway-based methods: HisCoM-PAGE, Global Test, GSEA, and CoxKM.</p><p><strong>Conclusion: </strong>HisCoM-KernelS successfully extends pathway-based analysis to survival outcomes, capturing complex nonlinear gene effects and inter-pathway correlations. Its application to the TCGA PDAC dataset emphasizes its utility in identifying biologically relevant pathways, offering a robust tool for survival phenotype research in high-throughput sequencing data.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345010","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":"Comparative analysis of the transcriptomes from regenerated plants and root explants of endangered Oplopanax elatus.","authors":"Ji Won Seo, Hong Ju Choi, Da Ye Ham, Jiu Park, Ik Young Choi, Chang Yeon Yu, Myong Jo Kim, Eun Soo Seong","doi":"10.1007/s13258-024-01566-y","DOIUrl":"https://doi.org/10.1007/s13258-024-01566-y","url":null,"abstract":"<p><strong>Background: </strong>Oplopanax elatus is a plant of therapeutic significance in oriental medicine; however, its mass cultivation is limited owing to the difficulties in propagating it from seeds.</p><p><strong>Methods: </strong>In this study, we investigated the transcriptome profiles and transcriptional regulatory factors expressed during plantlet regeneration from root tissues of the endangered O. elatus.</p><p><strong>Results: </strong>The RNA-seq results for the control and regenerated plants cultured in liquid medium for 8 weeks showed that the clean length of the control group was 11,901,667,912 and that of the 8-week sample was 10,115,155,171, indicating a clean value of 97% for both samples. The number of mapped paired-end reads was 63,922,480 for the control group and 54,146,902 for the 8-week sample. The number of genes for which at least one clean data point was mapped was 43,177 in the control group and 42,970 in the 8-week sample. The results of the differentially expressed gene analysis indicate that the number of upregulated genes in the 8-week sample was 158, and the number of downregulated genes was 424. Gene Ontology (GO) analysis of the upregulated genes revealed that GO terms were classified into 14 categories, and genes expressed in the biological process category occurred most frequently. GO terms of the downregulated genes were evenly distributed into two categories: biological process and molecular function. From the upregulated genes, eight reference genes with significant differences in expression were selected and analyzed using real-time PCR. The Oe38836 gene (late embryogenesis abundant protein M17-like isoform X1) showed the highest expression rate that was more than tenfold that of the control. Oe40610 (auxin-responsive protein SAUR21-like) and Oe07114 (glucose-1-phosphate adenyl transferase-like protein) genes showed expression levels that were increased eightfold relative to the control.</p><p><strong>Conclusions: </strong>The RNA sequencing (RNA-seq) results from the plants regenerated through liquid culture of O. elatus root tissue were confirmed using real-time PCR, indicating their reliability.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345008","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":"Genome-wide analysis of the potato GRF gene family and their expression profiles in response to hormone and Ralstonia solanacearum infection.","authors":"Changhe Wei, Jinli Yan, Pan Xu, Xia Wu, Yan Yi, Xuemei Yue, Caiyan Chen, Lang Yan, Mengmeng Yin","doi":"10.1007/s13258-024-01572-0","DOIUrl":"https://doi.org/10.1007/s13258-024-01572-0","url":null,"abstract":"<p><strong>Background: </strong>Potato (Solanum tuberosum L.) is one of the most economically significant crops globally. Nevertheless, potato cultivation is becoming increasingly susceptible to a multitude of diseases, including bacterial wilt, which is caused by Ralstonia solanacearum.</p><p><strong>Objective: </strong>To identify the GRF gene family in potatoes and to examine their expression profiles in response to hormones and R. solanacearum infection.</p><p><strong>Methods: </strong>A comprehensive genome-wide analysis was conducted to identify the GRF gene family in the potato genome.</p><p><strong>Results: </strong>A total of 13 GRF genes were identified from the latest potato genome, including five StGRFs belonging to the ɛ group and eight of the non-ɛ group. The transcriptional responses of the StGRFs to two biotic stress-related phytohormones (SA and MeJA) were defined, as well as the response to infection with R. solanacearum in a bacterial wilt-sensitive cultivar, S. tuberosum 'Qingshu 9'. Many StGRF genes exhibited high induction levels in response to R. solanacearum infection and SA treatment while displaying a marked decline in expression in the presence of MeJA. Furthermore, protein interaction network analysis revealed that the StGRF proteins interact with several candidate target proteins, indicating that GRF proteins are ubiquitous regulators in potatoes. However, the associations between two type III effectors (T3Es) RipAC/RipH2 from R. solanacearum isolates and StGRF7 were not detectable in a yeast two-hybrid assay.</p><p><strong>Conclusion: </strong>This study provides comprehensive information on the GRF gene family and lays a foundation for further research on the molecular mechanism of potato biotic stress adaptation.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345009","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":"Association mapping analysis (AMA) for morpho-agronomic traits and leaf aromatic compounds using SSR markers in three types of Perilla crop collected from South Korea","authors":"Jungeun Cho, Hyeon Park, Tae Hyeon Heo, Ju Kyong Lee","doi":"10.1007/s13258-024-01567-x","DOIUrl":"https://doi.org/10.1007/s13258-024-01567-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Perilla is a representative leafy vegetable in South Korea. As K-Food (Korean food) is in the spotlight around the world, there is also increasing interest in Western countries in <i>Perilla</i> crop, an annual plant belonging to the Lamiaceae family.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To discover comprehensive information, including genetic and phylogenetic relationships among the 80 native <i>Perilla</i> accessions, using three types of data: simple sequence repeat (SSR) marker data, volatiles profile data, and morpho-agronomic data.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study conducted genotypic and phenotypic analyses on 80 <i>Perilla</i> accessions of three types (cultivated var. <i>frutescens</i>, weedy var. <i>frutescens</i>, weedy var. <i>crispa</i>) from South Korea. Five groups (G1-G5) of the 80 <i>Perilla</i> accessions of the three types were differentiated into two different clusters [genotype-based clustering (GTC) and phenotype-based clustering (PTC)] based on an aroma sensory phenotypic test.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 314 alleles were confirmed using 55 <i>Perilla</i> SSR primer sets, and genetic variation in the 80 <i>Perilla</i> accessions was evaluated. Among the three statistical analysis methods, principal coordinate analysis (PCoA) and GTC using data of the 55 <i>Perilla</i> SSR markers revealed perfectly consistent results, whereas PTC produced a total of six clusters. The 10 <i>Perilla</i> SSR markers associated with and significantly correlated with both biochemical and morphological characteristics were selected.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These findings are expected to provide valuable information for developing global South Korean <i>Perilla</i> cultivars for further studies in <i>Perilla</i> crop breeding programs.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261657","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":"Recent advances in anticancer mechanisms of molecular glue degraders: focus on RBM39-dgrading synthetic sulfonamide such as indisulam, E7820, tasisulam, and chloroquinoxaline sulfonamide","authors":"Ji Hoon Jang, Joo-Young Kim, Tae-Jin Lee","doi":"10.1007/s13258-024-01565-z","DOIUrl":"https://doi.org/10.1007/s13258-024-01565-z","url":null,"abstract":"<p>Synthetic sulfonamide anticancer drugs, including E7820, indisulam, tasisulam, and chloroquinoxaline sulfonamide, exhibit diverse mechanisms of action and therapeutic potential, functioning as molecular glue degraders. E7820 targets RBM39, affecting RNA splicing and angiogenesis by suppressing integrin α2. Phase I studies have demonstrated some stability in advanced solid malignancies; however, further efficacy studies are required. Indisulam causes G1 cell cycle arrest and delays the G1/S transition by modulating splicing through RBM39 degradation via DCAF15. Despite its limited initial efficacy, it shows promise in combination therapies, particularly for hematopoietic malignancies and gliomas. Tasisulam inhibits VEGF signaling, suppresses angiogenesis, and induces apoptosis. Although early trials indicated broad activity, safety concerns have halted its development. Chloroquinoxaline sulfonamide, initially investigated for cell cycle arrest and topoisomerase II inhibition, was discontinued owing to its limited efficacy and toxicity, despite promising initial results. Recent studies revealed the structural interaction of E7820 with DCAF15 and RBM39, although phase II trials on myeloid malignancies have shown limited efficacy. Indisulam is effective against glioblastoma and neuroblastoma, with potential synergy in combination therapies and metabolic disruption. Recent research on tasisulam reveals its potential in cancer therapy by targeting RBM39 degradation through DCAF15-mediated pathways. Understanding these mechanisms could lead to new treatments that affect alternative splicing and improve cancer therapies Overall, although these drugs exhibit promising mechanisms of action, further research is required to optimize their clinical efficacy and safety.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261714","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":"Roles and action mechanisms of NRIP1 in pre-eclampsia","authors":"Fangle Gu, Yanxin Zhang, Yujie Sun, Yan Liu, Liying Zhang, Dan Lu","doi":"10.1007/s13258-024-01563-1","DOIUrl":"https://doi.org/10.1007/s13258-024-01563-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Pre-eclampsia (PE) is characterized by the onset of hypertension and proteinuria during pregnancy. Here, we aimed to explore the functions of nuclear receptor-interacting protein 1 (NRIP1) in PE mice and human placental JEG-3 cells. We evaluated its effects on JEG-3 cell proliferation, apoptosis, invasion, and inflammatory response and regulation of Wnt/β-catenin pathway.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>NRIP1 levels in human serum and placental tissues, JEG-3 cells, and mouse models were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. JEG-3 cell growth, apoptosis, migration, and invasion were evaluated via 5-ethynyl-2’-deoxyuridine, flow cytometry, and transwell assays. Levels of the inflammatory factors, matrix metalloproteinase (MMP)-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were determined via enzyme-linked immunosorbent assay. Wnt/β-catenin pathway was assessed via western blotting and qRT-PCR. Systolic blood pressure and proteinuria were measured using the non-invasive tail cuff method and Coomassie brilliant blue assay, respectively. TdT-mediated dUTP nick-end labeling assay was used to assess cell apoptosis in the placental tissues of PE mice.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>NRIP1 levels were upregulated in the serum and placental tissues of patients with PE. In vitro experiments revealed that NRIP1-small interfering RNA (siRNA) increased the cell viability, migration, and invasion and reduced the cell apoptosis compared to the control siRNA. Moreover, NRIP1-siRNA activated the Wnt/β-catenin signaling pathway, as indicated by the increased Wnt3a, β-catenin, p-glycogen synthase kinase-3β, c-Myc, and cyclin D1 levels. Levels of the inflammatory factors, IL-6, TNF-α, and MMP-2, were decreased in the NRIP1-siRNA-treated group. Notably, NRIP1 downregulation improved the PE-like symptoms, inhibited the inflammatory responses, and reduced apoptosis in PE mice.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study revealed the crucial roles of NRIP1 in PE. Our findings revealed that NRIP1 downregulation relieved PE symptoms by inhibiting cell proliferation, migration, and invasion via the Wnt/β-catenin pathway, thus providing a novel candidate for PE treatment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261658","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}