Biology Direct最新文献

{"title":"Utilizing liquid-liquid biopolymer regulators to predict the prognosis and drug sensitivity of hepatocellular carcinoma.","authors":"Jianhao Li, Han Chen, Lang Bai, Hong Tang","doi":"10.1186/s13062-025-00592-4","DOIUrl":"https://doi.org/10.1186/s13062-025-00592-4","url":null,"abstract":"<p><strong>Background: </strong>Liquid-liquid phase separation (LLPS) is essential for the formation of membraneless organelles and significantly influences cellular compartmentalization, chromatin remodeling, and gene regulation. Previous research has highlighted the critical function of liquid-liquid biopolymers in the development of hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This study conducted a comprehensive review of 3,685 liquid-liquid biopolymer regulators, leading to the development of a LLPS related Prognostic Risk Score (LPRS) for HCC through bootstrap-based univariate Cox, Random Survival Forest (RSF), and LASSO analyses. A prognostic nomogram for HCC patients was developed using LPRS and other clinicopathological factors. We utilized SurvSHAP to identify key genes within the LPRS influencing HCC prognosis. To validate our findings, we collected 49 HCC cases along with adjacent tissue samples and confirmed the correlation between DCAF13 expression and HCC progression through qRT-PCR analysis and in vitro experiments.</p><p><strong>Results: </strong>LPRS was established with 8 LLPS-related genes (TXN, CBX2, DCAF13, SLC2A1, KPNA2, FTCD, MAPT, and SAC3D1). Further research indicated that a high LPRS is closely associated with vascular invasion, histological grade (G3-G4), and TNM stage (III-IV) in HCC, concurrently establishing LPRS as an independent risk factor for prognosis. A nomogram that integrates LPRS with TNM staging and patient age markedly improves the predictive accuracy of survival outcomes for HCC patients. Our findings suggest that increased DCAF13 expression in HCC plays a crucial role in cancer progression and angiogenesis. Navitoclax has emerged as a promising treatment for HCC patients with high LPRS levels, offering a novel therapeutic direction by targeting LLPS.</p><p><strong>Conclusion: </strong>We have formulated a novel LPRS model that is capable of accurately predicting the clinical prognosis and drug sensitivity of HCC. DCAF13 might play a pivotal role in malignant progression mediated by LLPS.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"2"},"PeriodicalIF":5.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating multi-layered biological priors to improve genomic prediction accuracy in beef cattle.","authors":"Zhida Zhao, Qunhao Niu, Jiayuan Wu, Tianyi Wu, Xueyuan Xie, Zezhao Wang, Lupei Zhang, Huijiang Gao, Xue Gao, Lingyang Xu, Bo Zhu, Junya Li","doi":"10.1186/s13062-024-00574-y","DOIUrl":"10.1186/s13062-024-00574-y","url":null,"abstract":"<p><strong>Background: </strong>Integrating multi-layered information can enhance the accuracy of genomic prediction for complex traits. However, the improvement and application of effective strategies for genomic prediction (GP) using multi-omics data remains challenging.</p><p><strong>Methods: </strong>We generated 11 feature sets for sequencing variants from genomics, transcriptomics, metabolomics, and epigenetics data in beef cattle, then we assessed the contribution of functional variants using genomic restricted maximum likelihood (GREML). We next estimated and ranked variant scores for 43 economically important traits, and compared the prediction accuracy of the top and bottom sets using genomic best linear unbiased prediction (GBLUP) and BayesB model. In addition, we annotated the variants from GWAS with functional feature sets and performed enrichment analysis.</p><p><strong>Results: </strong>We observed significant enrichments for 32 functional categories in 11 feature sets. The evolutionary related sets (conservation regions and selection signatures) contributed significantly to heritability (31.78-fold and 14.48-fold enrichment), while metabolomics and transcriptomics showed low heritability enrichments. We observed a significant increase in prediction accuracy using the top feature set variants compared to whole-genome sequencing (WGS) data. The prediction accuracy based on the top 10% variant set showed an average increase of 11.6% and 7.54% using BayesB and GBLUP across traits, respectively. Notably, the greatest increase of 31.52% was obtained for spleen weight (SW) using BayesB. Also, we found that the top 10% of variants show strong enrichment with weight related QTLs based on the Cattle QTL database.</p><p><strong>Conclusions: </strong>Our findings suggest that integrating biological prior information from multiple layers can enhance our understanding of the genetic architecture underlying complex traits and further improve genomic prediction in beef cattle.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"147"},"PeriodicalIF":5.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.","authors":"Massimiliano Agostini, Erica Giacobbi, Francesca Servadei, Julia Bishof, Likas Funke, Giuseppe Sica, Valentina Rovella, Marco Carilli, Valerio Iacovelli, Yufang Shi, Jianquan Hou, Eleonora Candi, Gerry Melino, Giulio Cervelli, Manuel Scimeca, Alessandro Mauriello, Pierluigi Bove","doi":"10.1186/s13062-024-00492-z","DOIUrl":"10.1186/s13062-024-00492-z","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.</p><p><strong>Results: </strong>We have observed deletion of KDM6A gene, which may represent an additional genomic alteration to be considered for patient stratification. The cancer hallmarks gene signatures highlight intriguing molecular aspects that characterize the biology of this tumor by both a high hypoxia and immune infiltration scores. Moreover, our analysis showed a slight increase in the Tumoral Mutational Burden, as well as an over-expression of the immune checkpoints. The omics profiling integrating hypoxia, ROS and the anti-cancer immune response, optimizes therapeutic strategies and advances personalized care for prostate cancer patients.</p><p><strong>Conclusion: </strong>The here data reported can lay the foundation for predicting a poor prognosis for the studied prostate cancer, as well as the possibility of targeted therapies based on the modulation of hypoxia, ROS, and the anti-cancer immune response.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"146"},"PeriodicalIF":5.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular mechanism of estrogen therapy effectiveness after TCRA in IUA patients at single-cell level.","authors":"Yue Du, Ruzhen Shuai, Sang Luo, Yiran Jin, Fengjuan Xu, Jingyi Zhang, Dan Liu, Limin Feng","doi":"10.1186/s13062-024-00583-x","DOIUrl":"10.1186/s13062-024-00583-x","url":null,"abstract":"<p><strong>Background: </strong>Intrauterine adhesion (IUA) is a common cause of clinically refractory infertility, and there exists significant heterogeneity in the treatment outcomes among IUA patients with the similar severity after transcervical resection of adhesion(TCRA). The underlying mechanism of different treatment outcomes occur remains elusive, and the precise contribution of various cell subtypes in this process remains uncertain.</p><p><strong>Results: </strong>Here, we performed single-cell transcriptome sequencing on 10 human endometrial samples to establish a single-cell atlas differences between patients who responded to estrogen therapy and those who did not. The results showed increased infiltration of immune cells such as monocyte macrophages, T cells, and natural killer (NK) cells in patients who did not respond to estrogen therapy. Our findings indicate that distinct fibroblast subsets are implicated in the modulation of the Wnt, Hippo, and Hedgehog signaling pathways, as evidenced by functional enrichment analyses. This may have implications for the therapeutic efficacy in patients with IUA. Furthermore, we delineated the markers and transcriptional status of different macrophage subsets and identified two cell clusters, CXCL10high and CCL4L2high macrophage subsets, which are intimately associated with inflammation and fibrosis. The state of fibrosis and inflammatory response in human endometrial tissues with disparate treatment outcomes is revealed, and providing evidence to clarify the underlying determinants of sensitivity to estrogen therapy.</p><p><strong>Conclusions: </strong>We described the transcriptional status of different cell subtypes in the two groups of patients, providing new ideas for exploring the molecular mechanism of the difference in the effectiveness of estrogen therapy in patients, and providing theoretical basis for providing precise and individualized treatment plans for IUA patients.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"142"},"PeriodicalIF":5.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals the critical role of alternative splicing in cattle testicular spermatagonia.","authors":"Xiuge Wang, Chunhong Yang, Xiaochao Wei, Yaran Zhang, Yao Xiao, Jinpeng Wang, Qiang Jiang, Zhihua Ju, Yaping Gao, Yanqin Li, Yundong Gao, Jinming Huang","doi":"10.1186/s13062-024-00579-7","DOIUrl":"10.1186/s13062-024-00579-7","url":null,"abstract":"<p><p>Spermatogonial stem cells (SSCs) form haploid gametes through the precisely regulated process of spermatogenesis. Within the testis, SSCs undergo self-renewal through mitosis, differentiation, and then enter meiosis to generate mature spermatids. This study utilized single-cell RNA sequencing on 26,888 testicular cells obtained from five Holstein bull testes, revealing the presence of five distinct germ cell types and eight somatic cell types in cattle testes. Gene expression profiling and enrichment analysis were utilized to uncover the varied functional roles of different cell types involved in cattle spermatogenesis. Additionally, unique gene markers specific to each testicular cell type were identified. Moreover, differentially expressed genes in spermatogonia exhibited notable enrichment in GO terms and KEGG pathway linked to alternative splicing. Notably, our study has shown that the activity of the YY1 regulation displays distinct expression patterns in spermatogonia, specifically targeting spliceosome proteins including RBM39, HNRNPA2B1, HNRNPH3, CPSF1, PCBP1, SRRM1, and SRRM2, which play essential roles in mRNA splicing. These results emphasize the importance of mRNA processing in spermatogonia within cattle testes, providing a basis for further investigation into their involvement in spermatogonial development.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"145"},"PeriodicalIF":5.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced itaconic acid secretion from macrophages mediates the protection of mesenchymal stem cell-derived exosomes on lipopolysaccharide-induced acute lung injury mice.","authors":"Yanmei Wen, Zong'an Liang","doi":"10.1186/s13062-024-00586-8","DOIUrl":"10.1186/s13062-024-00586-8","url":null,"abstract":"<p><strong>Background: </strong>Alveolar macrophages (AMs) is critical to exacerbate acute lung injury (ALI) induced by lipopolysaccharide (LPS) via inhibiting inflammation, which could by shifted by mesenchymal stem cell-derived exosomes (MSC-exos). But the underlying rationale is not fully clarified. Our study aimed to analyze the significance of itaconic acid (ITA) in mediating the protective effects of MSC-exos on LPS-induced ALI.</p><p><strong>Methods: </strong>MSC-exos were used to treat pulmonary microvascular endothelial cells (PMVECs) co-cultured with AMs under LPS stimulation. si-IRG1 was transfected to AMs. PMVEC permeability, apoptosis rates, and inflammatory cytokine levels were assessed. In vivo, C57BL/6 wild-type (WT) and Irg1-/- mice were employed to explore the protection of MSC-exos against LPS-induced ALI. The lung injury was determined by histological and biochemical assays. ITA levels were measured using gas chromatography-mass spectrometry. Western blot and flow cytometry analyses were performed to assess M1/M2 polarization.</p><p><strong>Results: </strong>Co-culture with AMs significantly increased PMVEC permeability, apoptosis rates, IL-6, TNF-α levels and Claudin-5 and ZO-1 expression induced by LPS treatment, which were attenuated by MSC-exos accompanied by enhanced ITA level. After si-IRG1 transfection, MSC-exos' protective efficacy was reversed, with suppressed M2 polarization. In vivo, MSC-exos alleviated alveolar structure disruption, pulmonary edema, inflammation and increased ITA concentration in WT mice but had reduced effects in Irg1-/- mice, with neglected M2 polarization.</p><p><strong>Conclusions: </strong>ITA secretion facilitated the MSC-exos' protective benefits on LPS-induced PMVEC damage and ALI in mice by promoting AM M2 polarization, highlighting a potential therapeutic strategy for ALI and related inflammatory lung diseases.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"138"},"PeriodicalIF":5.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP44 regulates HEXIM1 stability to inhibit tumorigenesis and metastasis of oral squamous cell carcinoma.","authors":"Shuai Chen, Kefan Wu, Yingrui Zong, Zhenzhen Hou, Zhifen Deng, Zongping Xia","doi":"10.1186/s13062-024-00573-z","DOIUrl":"10.1186/s13062-024-00573-z","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is the most frequent type of oral malignancy with high metastasis and poor prognosis. The deubiquitinating enzyme Ubiquitin Specific Peptidase 44 (USP44) regulates the mitotic checkpoint, and its deficiency leads to aneuploidy and increases tumor incidence. However, the role of USP44 in OSCC is not well understood. Herein, we analyzed mRNA sequencing data of OSCC samples downloaded from the TCGA and GEO databases and found that USP44 was decreased in human OSCC tissues and was positively correlated to the survival of OSCC patients. To investigate the biological impact of USP44, we used recombinant lentiviruses to overexpress or knockdown USP44 expression in OSCC cell lines, which were also injected subcutaneously or into the lateral tail vein of Male BALB/c nude mice to model tumorigenesis or lung metastasis in vivo, respectively. The results showed that overexpression of USP44 inhibited malignant cell phenotypes in vitro and suppressed tumor growth and lung metastasis in vivo, while its downregulation had the opposite effects. Comprehensive proteomic analyses through Co-IP mass spectrometry and label-free quantitative LC-MS/MS methods identified 112 differentially expressed proteins positively regulated by USP44, among which 13 were involved in cancer-related pathways including apoptotic signaling and cell cycle regulation. PPI analysis identified Hexamethylene Bis-Acetamide-Inducible Protein 1 (HEXIM1) as the hub protein. Upregulation of USP44 enhanced HEXIM1 protein stability, leading to its higher expression in OSCC cells. Silencing of HEXIM1 further enhanced the malignant phenotype of OSCC cells. At the same time, HEXIM1 knockdown reversed the antitumor effects of USP44. These findings demonstrated that USP44 acted as a critical tumor suppressor in OSCC by inhibiting cell proliferation and metastasis through the stabilization of HEXIM1 protein, suggesting that USP44-HEXIM1 axis is a promising target for OSCC therapy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"143"},"PeriodicalIF":5.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTGES3 proteolysis using the liposomal peptide-PROTAC approach.","authors":"Shiwei Liu, Fukang Yuan, Hui Dong, Jiaqi Zhang, Xinyu Mao, Yangsui Liu, Huansong Li","doi":"10.1186/s13062-024-00580-0","DOIUrl":"10.1186/s13062-024-00580-0","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, and the lack of effective biomarkers for early detection leads to poor therapeutic outcomes. Prostaglandin E Synthase 3 (PTGES3) is a putative prognostic marker in many solid tumors; however, its expression and biological functions in HCC have not been determined. The proteolysis-targeting chimera (PROTAC) is an established technology for targeted protein degradation. Compared to the small-molecule PROTAC, the peptide PROTAC (p-PROTAC) utilizes peptides bound to target proteins to mediate the ubiquitination and degradation of undruggable proteins. This study aimed to use the PROTAC technology to develop a PTGES3 degrader liposome complex containing a PTGES3-binding peptide and the E3 ubiquitin ligase ligand pomalidomide for regulating cell function and provide a novel pathway for treating HCC.</p><p><strong>Results: </strong>In this study, we demonstrated that PTGES3 is highly expressed in HCC at the transcriptional and protein levels; furthermore, PTGES3 was identified as a novel drug target that could potentially treat HCC. Hence, we developed PTGES3-PROTACs by adjusting the ligand ratio to optimize the efficacy of degradation agents. The results revealed that PTGES3-PROTAC effectively degraded PTGES3 protein and strongly weakened the HCC malignant phenotype in vitro and in vivo.</p><p><strong>Conclusions: </strong>Our findings revealed that the highly selective PTGES3 proteolysis is a potential therapeutic strategy for HCC, and PTGES3 degraders PTGES3-PROTACs can be developed as safe and effective drugs for HCC treatment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"144"},"PeriodicalIF":5.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC01094 promotes gastric cancer through dual targeting of CDKN1A by directly binding RBMS2 and HDAC1.","authors":"Xinyi Zhou, Cheng Gu, Linmei Xiao, Li Hu, Guanhua Chen, Fei Zuo, Hongan Shao, Bojian Fei","doi":"10.1186/s13062-024-00582-y","DOIUrl":"10.1186/s13062-024-00582-y","url":null,"abstract":"<p><strong>Background: </strong>Accumulating studies have focused on long noncoding RNAs (lncRNAs) because of their regulatory effects on multiple cancers. However, the biological functions and molecular mechanisms of lncRNAs in gastric cancer (GC) remain to be elucidated in depth.</p><p><strong>Methods: </strong>Long intergenic nonprotein coding RNA 1094 (LINC01094), a differentially expressed lncRNA between GC tissues and adjacent normal tissues, was identified. Moreover, gain- and loss-of-function experiments in vitro and in vivo were carried out. To understand the mechanisms underlying the regulatory effects of LINC01094, we performed RNA pull-down assays, RNA immunoprecipitation assays, chromatin immunoprecipitation assays, luciferase reporter assays, etc. RESULTS: LINC01094 was markedly upregulated in GC tissues and cell lines, and LINC01094 upregulation was positively correlated with GC malignant behaviours in vitro and in vivo. Mechanistically, LINC01094 downregulated the expression of CDKN1A by interacting with RNA binding motif single stranded interacting protein 2 (RBMS2) and histone deacetylase 1 (HDAC1). Additionally, LINC01094 was confirmed to sponge miR-128-3p and participate in the LINC01094-miR-128-3p-RUNX family transcription factor 1 (RUNX1) feedback loop. Finally, Ro 5-3335, a validated RUNX1 inhibitor, was explored for anticancer drug development in GC.</p><p><strong>Conclusions: </strong>The LINC01094-miR-128-3p-RUNX1 feedback loop downregulates CDKN1A and promotes GC cooperatively with RBMS2 and HDAC1. Furthermore, Ro 5-3335 may hold promising therapeutic potential in the treatment of GC. Hence, our study found an oncogenic lncRNA, LINC01094, which could be a promising target for cancer treatment and diagnosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"137"},"PeriodicalIF":5.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Mendelian randomization and single-cell RNA-sequencing analyses identified OAS1 as a novel therapeutic target for erectile dysfunction via targeting fibroblasts.","authors":"Yi Wang, Guihua Chen, Deng Li","doi":"10.1186/s13062-024-00587-7","DOIUrl":"10.1186/s13062-024-00587-7","url":null,"abstract":"<p><p>Clinically, phosphodiesterase type 5 inhibitors (PDE5-Is) remain the first-line therapy for erectile dysfunction (ED) patients; however, approximately 35% of these patients are still failing to respond to the therapeutic effects. So, urgent needs are required to identify novel therapeutic targets for ED. Hence, in this report, it was the first time for us to integrate single-cell RNA-sequencing (scRNA-Seq), mendelian randomization (MR) analysis with expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data to find new treatment targets for ED. Disease-causing changes were revealed by MR analysis, and it showed that the OAS1 eQTL/cis-eQTL/cis-pQTL was causally related to ED, significantly reducing its risks (all P < 0.05). Disease-induced changes were revealed by scRNA-Seq, and it suggested that OAS1 mainly played its role in ED via targeting fibroblasts. We further concluded that the positive regulation of OAS1 gene expression could lead to the vicious circle of ED. As a result, drugs targeting OAS1 in the future might provide more potential opportunities and flexibility for treating ED. In conclusion, our study identified OAS1 as a gene of interest in the context of ED via targeting fibroblasts through integrated MR and scRNA-Seq analyses. While these findings highlighted the potential of OAS1 as a therapeutic target, further experimental and clinical studies were still required to validate its functional role and therapeutic relevance in ED pathology.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"136"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}