Biology Direct最新文献

{"title":"Comprehensive pan-cancer analysis indicates UCHL5 as a novel cancer biomarker and promotes cervical cancer progression through the Wnt signaling pathway.","authors":"Lingling Bao, Yuefei Wu, Zhengting Ren, Yi Huang, Yue Jiang, Kailang Li, Xin Xu, Yingquan Ye, Zhongxuan Gui","doi":"10.1186/s13062-024-00588-6","DOIUrl":"https://doi.org/10.1186/s13062-024-00588-6","url":null,"abstract":"<p><strong>Background: </strong>UCHL5 was initially recognized as a multifunctional molecule. While recent research has highlighted its involvement in tumor malignant biological behaviors, its specific role in promoting tumor cell apoptosis has drawn particular attention. However, the precise relationship between UCHL5 and various tumor types, as well as its influence within the immune microenvironment, remains unclear.</p><p><strong>Methods: </strong>The transcriptomic data and clinicopathological parameters across 33 cancer types were obtained from TCGA. Clinical pathological parameters of tumor patients, including gender, age, survival time, and staging, are utilized to evaluate the association between UCHL5 and pan-cancer characteristics. The prognostic significance of UCHL5 was evaluated through Cox analysis and Kaplan-Meier (K-M) methods. Protein expression data for UCHL5 were obtained from The Human Protein Atlas database, and its subcellular localization was further investigated. Additionally, potential correlations between UCHL5 and factors such as tumor-infiltrating immune cells, immunomodulators, microsatellite instability (MSI), and tumor mutation burden (TMB) were explored. The relationship between UCHL5 and immunotherapy efficacy was also assessed in independent cohorts, including IMvigor210, GSE78220, GSE67501, and GSE168204. Finally, the impact of UCHL5 on the malignant biological behavior of cervical cancer cells was investigated through in vitro experiments, along with an exploration of the underlying mechanisms.</p><p><strong>Results: </strong>We observed that UCHL5 expression levels were elevated in 11 types of cancer tissues compared to their corresponding normal tissues, while levels were lower in five tumor types. Additionally, UCHL5 expression displayed a significant correlation with tumor stage in BRCA, KIRC, LUAD, and TGCT. Cox and K-M analysis indicated that UCHL5 expression was significantly associated with prognosis in KIRC, KICH, CESC, ACC, and UVM. UCHL5 expression was negatively associated with stromal and immune scores in certain cancers. In terms of immune cell infiltration, UCHL5 expression in UCEC, SKCM, and COAD showed a negative correlation with regulatory T cells (Tregs). Furthermore, UCHL5 was widely associated with three types of immunomodulators. It also demonstrated a significant relationship with MSI and TMB in certain cancers and was connected to the immunotherapy efficacy. Finally, in vitro experiments confirmed that UCHL5 knockout enhances apoptosis in cervical cancer cells and disrupts Wnt/β-catenin signaling.</p><p><strong>Conclusions: </strong>Pan-cancer analysis indicates that UCHL5 is dysregulated in various tumor tissues and is closely associated with survival prognosis, the tumor immune microenvironment, and the efficacy of immunotherapy in certain cancer types. UCHL5 shows promise as a predictive biomarker, and its specific regulatory mechanisms across different cancers warrant further invest","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"139"},"PeriodicalIF":5.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostatitis, benign prostatic hyperplasia, and prostate cancer: a bidirectional Mendelian randomization study and clinical implications for these patients' populations.","authors":"Yi Wang, Guihua Chen, Deng Li, Dongliang Zhang, Qianwei Xing","doi":"10.1186/s13062-024-00575-x","DOIUrl":"https://doi.org/10.1186/s13062-024-00575-x","url":null,"abstract":"<p><strong>Background: </strong>No authoritative books or guidelines are currently available for revealing the interrelationships of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Moreover, no consensus on this issue has been reached among previously published epidemiological studies or meta-analyses.</p><p><strong>Purpose: </strong>We first took advantage of Mendelian randomization to clarify this issue and provide clinical implications for these patients' populations.</p><p><strong>Methods: </strong>Bidirectional two-sample and mediator Mendelian randomization were applied to explore the causal relationships among prostatitis, BPH, and PCa. Sensitivity analyses, including phenotype scanning, heterogeneity, pleiotropy, leave-one-out analysis, and the Steiger test, were conducted to evaluate the robustness and reliability of our results.</p><p><strong>Results: </strong>Our results revealed the interrelationships among prostatitis, BPH, and PCa via Mendelian randomization, confirming that genetic susceptibility to prostatitis or BPH could lead to increased risks of PCa directly or indirectly (P < 0.05). Moreover, mediator Mendelian randomization revealed four potential mediator pathways, including the prostatitis-BPH-PCa, the BPH-PCa-prostatitis, the PCa-prostatitis-BPH, and the PCa-BPH-prostatitis pathways. Based on these, we also provided clinical implications for prostatitis, BPH, and PCa patients' populations, respectively. Interestingly, a total of three vicious circles were revealed by us, including the prostatitis-BPH circle, the BPH-PCa circle, and the prostatitis-BPH-PCa circle. All of these three vicious circles contributed to the progression of benign prostate diseases to malignant diseases.</p><p><strong>Conclusion: </strong>We successfully clarified the interrelationships among prostatitis, BPH, and PCa, providing clinical implications for these patients' populations. A total of three vicious circles were also revealed by us to provide novel ideas for future drug development and guide clinical decision-making.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"129"},"PeriodicalIF":5.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploration into the diagnostic capabilities of microRNAs for myocardial infarction using machine learning.","authors":"Mehrdad Samadishadlou, Reza Rahbarghazi, Kaveh Kavousi, Farhad Bani","doi":"10.1186/s13062-024-00543-5","DOIUrl":"10.1186/s13062-024-00543-5","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) have shown potential as diagnostic biomarkers for myocardial infarction (MI) due to their early dysregulation and stability in circulation after MI. Moreover, they play a crucial role in regulating adaptive and maladaptive responses in cardiovascular diseases, making them attractive targets for potential biomarkers. However, their potential as novel biomarkers for diagnosing cardiovascular diseases requires systematic evaluation.</p><p><strong>Methods: </strong>This study aimed to identify a miRNA biomarker panel for early-stage MI detection using bioinformatics and machine learning (ML) methods. miRNA expression data were obtained for early-stage MI patients and healthy controls from the Gene Expression Omnibus. Separate datasets were allocated for training and independent testing. Differential expression analysis was performed to identify dysregulated miRNAs in the training set. The least absolute shrinkage and selection operator (LASSO) was applied for feature selection to prioritize relevant miRNAs associated with MI. The selected miRNAs were used to develop ML models including support vector machine, Gradient Boosted, XGBoost, and a hard voting ensemble (HVE).</p><p><strong>Results: </strong>Differential expression analysis discovered 99 dysregulated miRNAs in the training set. LASSO feature selection prioritized 21 miRNAs. Ten miRNAs were identified in both the LASSO subset and independent test set. The HVE model trained with the selected miRNAs achieved an accuracy of 0.86 and AUC of 0.83 on the independent test set.</p><p><strong>Conclusions: </strong>An integrated framework for robust miRNA selection from omics data shows promise for developing accurate diagnostic models for early-stage MI detection. The HVE model demonstrated good performance despite differences between training and test datasets.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"127"},"PeriodicalIF":5.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806237","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 Circle-Seq with transcriptomics reveals genome-wide characterization of extrachromosomal circular DNA for dilated cardiomyopathy.","authors":"Zhenhao Lin, Fangjie Dai, Bo Li, Yongchao Zhao, Changqian Wang","doi":"10.1186/s13062-024-00556-0","DOIUrl":"10.1186/s13062-024-00556-0","url":null,"abstract":"<p><strong>Background: </strong>Extrachromosomal circular DNAs (eccDNAs) are commonly found in various tumors and play a critical role in promoting oncogenesis. However, little is known about the characteristics and nature of eccDNAs in human heart failure. The aim of this study was to comprehensively analyze eccDNAs in human heart failure caused by dilated cardiomyopathy (DCM) and explore their potential functions.</p><p><strong>Methods: </strong>Circle-Seq and RNA-Seq were performed in cardiac tissue samples obtained from patients with DCM and healthy controls to identify eccDNAs and corresponding genes. Inward PCR, outward PCR and Sanger sequencing were conducted to validate the circular structure of eccDNAs. Bioinformatics was employed to probe the transcriptional activity of eccDNAs and their potential roles in the development of DCM. Ligase assisted minicircle accumulation strategy was used to synthesize a 500 bp circular DNA with a random sequence.</p><p><strong>Results: </strong>EccDNAs originated from all chromosomes, with the majority being less than 1 kb in size and about half containing genes or gene fragments. They were derived from specific repeat elements and primarily mapped to 5'UTR, 3'UTR, and CpG islands. Gene-rich chromosomes 17 and 19 exhibited higher eccDNA enrichment. Sequence motifs flanking eccDNA junction sites displayed frequent nucleotide repeats. The circular structure of eccDNAs were confirmed. Integration of Circle-Seq and RNA-Seq data identified that large eccDNAs can be directly transcribed in non-dividing cardiomyocytes, indicating their potential roles in gene expression. Small circular DNA elicited a stronger cytokine response than linear DNA with the same sequence.</p><p><strong>Conclusions: </strong>Our work provided a detailed profiling of eccDNAs in both healthy and DCM hearts and demonstrated the potential functions of both large and small eccDNAs. These findings enhance the comprehension of the role of eccDNAs in cardiac pathophysiology and establish a theoretical foundation for future investigations on eccDNAs in DCM.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"125"},"PeriodicalIF":5.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754736","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":"Soft X-ray tomography analysis of mitochondria dynamics in Saccharomyces cerevisiae.","authors":"Wei-Ling Huang, Chang-Lin Chen, Zi-Jing Lin, Chia-Chun Hsieh, Mo Da-Sang Hua, Chih-Chan Cheng, Tzu-Hao Cheng, Lee-Jene Lai, Chuang-Rung Chang","doi":"10.1186/s13062-024-00570-2","DOIUrl":"10.1186/s13062-024-00570-2","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria are highly dynamic organelles that constantly undergo processes of fission and fusion. The changes in mitochondrial dynamics shape the organellar morphology and influence cellular activity regulation. Soft X-ray tomography (SXT) allows for three-dimensional imaging of cellular structures while they remain in their natural, hydrated state, which omits the need for cell fixation and sectioning. Synchrotron facilities globally primarily use flat grids as sample carriers for SXT analysis, focusing on adherent cells. To investigate mitochondrial morphology and structure in hydrated yeast cells using SXT, it is necessary to establish a method that employs the flat grid system for examining cells in suspension.</p><p><strong>Results: </strong>We developed a procedure to adhere suspended yeast cells to a flat grid for SXT analysis. Using this protocol, we obtained images of wild-type yeast cells, strains with mitochondrial dynamics defects, and mutant cells possessing distinctive mitochondria. The SXT images align well with the results from fluorescent microscopy. Optimized organellar visualization was achieved by constructing three-dimensional models of entire yeast cells.</p><p><strong>Conclusions: </strong>In this study, we characterized the mitochondrial network in yeast cells using SXT. The optimized sample preparation procedure was effective for suspended cells like yeast, utilizing a flat grid system to analyze mitochondrial structure through SXT. The findings corresponded with the mitochondrial morphology observed under fluorescence microscopy, both in regular and disrupted dynamic equilibrium. With the acquired image of unique mitochondria in Δhap2 cells, our results revealed that intricate details of organelles, such as mitochondria and vacuoles in yeast cells, can be characterized using SXT. Therefore, this optimized system supports the expanded application of SXT for studying organellar structure and morphology in suspended cells.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"126"},"PeriodicalIF":5.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754737","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":"BRD4 sustains p63 transcriptional program in keratinocytes.","authors":"E Foffi, A Violante, R Pecorari, A M Lena, F Rugolo, G Melino, E Candi","doi":"10.1186/s13062-024-00547-1","DOIUrl":"10.1186/s13062-024-00547-1","url":null,"abstract":"<p><p>Here, we investigated the potential interaction between bromodomain-containing protein 4 (BRD4), an established epigenetic modulator and transcriptional coactivator, and p63, a member of the p53 transcription factor family, essential for epithelial development and skin homeostasis. Our protein-protein interaction assays demonstrated a strong and conserved physical interaction between BRD4 and the p53 family members-p63, p73, and p53-suggesting a shared binding region among these proteins. While the role of BRD4 in cancer development through its interaction with p53 has been explored, the effects of BRD4 and Bromodomain and Extra Terminal (BET) inhibitors in non-transformed cells, such as keratinocytes, remain largely unknown. Our functional analyses revealed changes in cellular proliferation and differentiation in keratinocytes depleted of either p63 or BRD4, which were further supported by using the BRD4 inhibitor JQ1. Transcriptomic analyses, chromatin immunoprecipitation, and RT-qPCR indicated a synergistic mechanism between p63 and BRD4 in regulating the transcription of keratinocyte-specific p63 target genes, including HK2, FOXM1, and EVPL. This study not only highlights the complex relationship between BRD4 and p53 family members but also suggests a role for BRD4 in maintaining keratinocyte functions. Our findings pave the way for further exploration of potential therapeutic applications of BRD4 inhibitors in treating skin disorders.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"124"},"PeriodicalIF":5.7,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738428","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":"Bone metabolism associated with annual antler regeneration: a deer insight into osteoporosis reversal.","authors":"Chunyi Li, Wenying Wang, Guokun Zhang, Hengxing Ba, He Liu, Jincheng Wang, Wei Li, Gerry Melino, Yufang Shi","doi":"10.1186/s13062-024-00561-3","DOIUrl":"10.1186/s13062-024-00561-3","url":null,"abstract":"<p><p>Osteoporosis, a metabolic disorder, remains challenging to treat due to limited understanding of its underlying mechanism. The annual cycle of \"cyclic physiological osteoporosis (CPO)\" and its full reversal in male deer represents a unique natural model for studying this condition. Deer antlers, weighing up to 25 kg/pair, derive over 60% of their mineral contents from deer skeleton during mineralization. Based on the literature, we propose to divide CPO and its reversal into two phases: Phase I (approximately 115 days): from hard antler casting to the end of antler linear growth, marked by simultaneous robust antler ossification and CPO development; and Phase II (up to 165 days): from end of Phase I to the onset of antler skin shedding, characterized by complete antler mineralization and CPO reversal. This review analyzes the paradoxical occurrence of robust antler ossification and skeleton CPO within the same endocrine microenvironment during phase I; total antler mineralization and full reversal of deer skeleton CPO in phase II. Furthermore, we will discuss potential insights for osteoporosis treatment using deer materials from the period of Phase II. Our goal is to identify novel substances and therapies that could be applied in clinical setting to effectively treat osteoporosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"123"},"PeriodicalIF":5.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726160","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":"YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway.","authors":"Bao Dai, Lei Xu, Shikuo Rong, Muye Song, Ziteng Lan, Weijian Chen, Lingyun Zhang, Yongchen Liu, Linhe Wang, Jinghua Li, Jian Chen, Zeyu Wu","doi":"10.1186/s13062-024-00566-y","DOIUrl":"10.1186/s13062-024-00566-y","url":null,"abstract":"<p><strong>Background: </strong>RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of the m6A reader YTH domain family 2 (YTHDF2) has not been reported in anaplastic thyroid cancer (ATC) and its biological mechanism is unclear.</p><p><strong>Methods: </strong>The relationship between YTHDF2 expression and ATC was determined using data sets and tissue samples. A range of analytical techniques were employed to investigate the regulatory mechanism of YTHDF2 in ATC, including bioinformatics analysis, m6A dot-blot analysis, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, RNA sequencing, RNA stability assays and dual luciferase reporter gene assays. In vitro and in vivo assays were also conducted to determine the contribution of YTHDF2 to ATC development.</p><p><strong>Results: </strong>YTHDF2 expression was significantly increased in ATC. The comprehensive in vitro and in vivo experiments demonstrated that YTHDF2 knockdown significantly attenuated ATC proliferation, invasion, migration, and apoptosis promotion, whereas YTHDF2 overexpression yielded the opposite trend. Mechanistically, RNA-seq, MeRIP-seq and RIP-seq analysis, and molecular biology experiments demonstrated that YTHDF2 accelerated the degradation of DNA damage-inducible transcript 4 or regulated in DNA damage and development 1 (DDIT4, or REDD1) mRNA in an m6A-dependent manner, which in turn activated the AKT/mTOR signaling pathway and induced activation of epithelial-mesenchymal transition (EMT), thereby promoting ATC tumor progression.</p><p><strong>Conclusions: </strong>This study is the first to demonstrate that elevated YTHDF2 expression levels suppress DDIT4 expression in an m6A-dependent manner and activate the AKT/mTOR signaling pathway, thereby promoting ATC progression. YTHDF2 plays a pivotal role in ATC progression, and it may serve as a promising therapeutic target in the future.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"122"},"PeriodicalIF":5.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726177","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":"miR-155 mediated regulation of PKG1 and its implications on cell invasion, migration, and apoptosis in preeclampsia through NF-κB pathway.","authors":"Xiaohua Luo, Xiaopei Guo, Ningning Chen, Rui Peng, Ci Pan, Zhuyin Li, Bing Zhao, Ruonan Ji, Siyu Li","doi":"10.1186/s13062-024-00526-6","DOIUrl":"10.1186/s13062-024-00526-6","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia (PE) is a severe pregnancy complication characterized by complex molecular interactions. Understanding these interactions is crucial for developing effective therapeutic strategies.</p><p><strong>Methods: </strong>This study applies a pharmacometabolomics approach to explore the roles of miR-155 and PKG1 in PE, focusing on the regulatory influence of the NF-κB signaling pathway. Blood metabolomic profiles were analyzed, and bioinformatics tools, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization were employed to determine the expression and function of miR-155 and PKG1. Cell invasion, migration, proliferation, and apoptosis assays were conducted to assess miR-155's modulation of PKG1. Additionally, RT-qPCR and WB analysis elucidated NF-κB-mediated regulation mechanisms.</p><p><strong>Results: </strong>Our findings indicate significant metabolic alterations associated with miR-155 modulation of PKG1, with NF-κB acting as a critical upstream regulator. The study demonstrates that miR-155 affects cellular functions such as invasion, migration, proliferation, and apoptosis through PKG1 modulation. Furthermore, the NF-κB signaling pathway regulates miR-155 expression, contributing to the pathological processes of PE.</p><p><strong>Conclusion: </strong>This study provides a proof of concept for using pharmacometabolomics to understand the molecular mechanisms of PE, suggesting new therapeutic targets and advancing personalized medicine approaches. These insights highlight the potential of pharmacometabolomics to complement genomic and transcriptional data in disease characterization and treatment strategies, offering new avenues for therapeutic intervention in PE.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"121"},"PeriodicalIF":5.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715398","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":"Combatting cellular immortality in cancers by targeting the shelterin protein complex.","authors":"Sohini Chakraborty, Satarupa Banerjee","doi":"10.1186/s13062-024-00552-4","DOIUrl":"10.1186/s13062-024-00552-4","url":null,"abstract":"<p><p>Shelterin proteins (TERF1, TERF2, TPP1, TINF2, POT1) protect telomeres, prevent unwarranted repair activation, and regulate telomerase activity. Alterations in these proteins can lead to cancer progression. This study uses an in-silico approach to examine shelterin in tumour samples across various cancers, employing mutation plots, phylogenetic trees, and sequence alignments. Network pharmacology identified TERF1 as an essential shelterin protein and transcription factors RUNX1, CTCF, and KDM2B as potential biomarkers due to their interactions with miRNAs and shelterin proteins. We performed MCODE analysis to identify subnetworks of ncRNAs interacting with the shelterin proteins. Shelterin expression predicted patient survival in 24 cancer types, with TERF1, TERF2, TINF2, and POT1 significantly expressed in testicular, AML, prostate, breast and renal cancers, respectively, and TPP1 in AML and skin cancer. Spearman and Pearson's analyses showed significant correlations of TERF1 across cancers, with near-significant correlations for all five proteins in different cancer datasets like breast cancer, kidney renal papillary and lung squamous cell carcinoma, skin cutaneous melanoma, etc.,. Shelterin expression correlated with patient survival in breast, renal, lung, skin, uterine, and gastric cancers. Insights into TPP1-associated glycans highlighted glycosylated sites contributing to tumorigenesis. This study provides molecular signatures for further functional and therapeutic research on shelterin, highlighting its potential as a target for anti-cancer therapies and promising prospects for cancer prognosis and prediction.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"120"},"PeriodicalIF":5.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692697","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}