Biology Direct最新文献

{"title":"The impact of androgen-induced translation in modulating androgen receptor activity.","authors":"Justus S Israel, Laura-Maria Marcelin, Sherif Mehralivand, Jana Scholze, Jörg Hofmann, Matthias B Stope, Martin Puhr, Christian Thomas, Holger H H Erb","doi":"10.1186/s13062-024-00550-6","DOIUrl":"10.1186/s13062-024-00550-6","url":null,"abstract":"<p><strong>Introduction: </strong>Dysregulated androgen receptor (AR) activity is central to various diseases, particularly prostate cancer (PCa), in which it drives tumour initiation and progression. Consequently, antagonising AR activity via anti-androgens is an indispensable treatment option for metastatic PCa. However, despite initial tumour remission, drug resistance occurs. Therefore, the AR signalling pathway has been intensively investigated. However, the role of AR protein stability in AR signalling and therapy resistance has not yet been deciphered. Therefore, this study aimed to investigate the role of AR protein changes in transactivity and assess its mechanism as a possible target in PCa.</p><p><strong>Methods: </strong>LNCaP, C4-2, and 22Rv1 cells were treated with R1881, enzalutamide, cycloheximide, and Rocaglamide. Mass spectrometry analyses were performed on LNCaP cells to identify the pathways enriched by the treatments. Western blotting was performed to investigate AR protein levels and localisation changes. Changes in AR transactivity were determined by qPCR.</p><p><strong>Results: </strong>Mass spectrometry analyses were performed on LNCaP cells to decipher the molecular mechanisms underlying androgen- and antiandrogen-induced alterations in the AR protein. Pathway analysis revealed the enrichment of proteins involved in different pathways that regulate translation. Translational and proteasome inhibitor experiments revealed that these AR protein changes were attributable to modifications in translational activity. Interestingly, the effects on AR protein levels in castration-resistant PCa (CRPC) cells C4-2 or enzalutamide-resistant cells 22Rv1 were less prominent and non-existent. This outcome was similarly observed in the alteration of AR transactivation, which was suppressed in hormone-sensitive prostate cancer (HSPC) LNCaP cells by translational inhibition, akin to the effect of enzalutamide. In contrast, treatment-resistant cell lines showed only a slight change in AR transcription.</p><p><strong>Conclusion: </strong>This study suggests that in HSPC, AR activation triggers a signalling cascade that increases AR protein levels by enhancing its translation rate, thereby amplifying AR activity. However, this mechanism appears to be dysregulated in castration-resistant PCa cells.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"111"},"PeriodicalIF":5.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614923","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":"LncRNA NORFA promotes the synthesis of estradiol and inhibits the apoptosis of sow ovarian granulosa cells through SF-1/CYP11A1 axis.","authors":"Zhennan Guo, Qiang Zeng, Qiqi Li, Baosen Shan, Yangan Huo, Xiaoli Shi, Qifa Li, Xing Du","doi":"10.1186/s13062-024-00563-1","DOIUrl":"10.1186/s13062-024-00563-1","url":null,"abstract":"<p><strong>Background: </strong>Biosynthesis of 17β-estradiol (E2) is a crucial ovarian function in mammals, which is essential for follicular development and pregnancy outcome. Exploring the epigenetic regulation of E2 synthesis is beneficial for maintaining ovary health and the optimal reproductive traits. NORFA is the first validated sow fertility-associated long non-coding RNA (lncRNA). However, its role on steroidogenesis is elusive. The aim of this study is to investigate the regulation and underlying mechanism of NORFA to E2 synthesis in sow granulosa cells (GCs).</p><p><strong>Results: </strong>Through Pearson correlation analysis and comparative detection, we found that NORFA expression was positively correlated with the levels of pregnenolone (PREG) and E2 in follicles, which also exhibited similar alteration patterns during follicular atresia. ELISA was conducted and indicated for the first time that NORFA induced the synthesis of PREG and E2 in sow GCs in a dose- and time-dependent manner. RNA-seq, GSEA and quantitative analyses results validated that CYP11A1, the coding gene of P450SCC which is the first step rate-limiting enzyme of E2 synthesis, was a positive functional target of NORFA. Mechanistically, NORFA promotes SF-1 expression by stabilizing NR5A1 mRNA through directly interacting with its 3'-UTR, and also tethers SF-1 to shuttle into nucleus. Additionally, SF-1 in the nucleus activates CYP11A1 transcription by directly binding to its promoter, which ultimately induces E2 synthesis and inhibits GC apoptosis.</p><p><strong>Conclusion: </strong>Our findings highlight that NORFA, a multifunctional lncRNA, induces E2 synthesis and inhibits GC apoptosis through the SF-1/CYP11A1 axis in a ceRNA-independent manner, which provide valuable clues and potential targets for follicular atresia inhibition and female fertility improvement.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"107"},"PeriodicalIF":5.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614850","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":"TRIM47 drives gastric cancer cell proliferation and invasion by regulating CYLD protein stability.","authors":"Jianguo Wang, Jing Ye, Rongqiang Liu, Chen Chen, Weixing Wang","doi":"10.1186/s13062-024-00555-1","DOIUrl":"10.1186/s13062-024-00555-1","url":null,"abstract":"<p><p>The expression of TRIM47, a member of the TRIM protein and E3 ubiquitin ligase families, is elevated in various cancers, such as non-small cell lung cancer and colorectal cancer, and is linked to poor prognosis. This study aimed to investigate the role of TRIM47 in gastric cancer development. Using The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset and analysis of 20 patient samples from our center, TRIM47 was found to be significantly up-regulated in gastric cancer tissues and associated with advanced N-stage and poor prognosis. We constructed stable TRIM47 knockdown and overexpressing gastric cancer cell lines. CCK8, EDU, colony formation, wound healing, and Transwell tests were used to evaluate the effects on cell proliferation, invasion, and migration. The results showed that TRIM47 knockdown inhibited the proliferation, migration and invasion of gastric cancer cells, while TRIM47 overexpression promoted these behaviors. These results were further confirmed in vivo. In the mechanism part, we found that TRIM47 interacts with CYLD protein. Moreover, TRIM47 promotes K48-linked ubiquitination, leading to the degradation of CYLD by the proteasome, thereby activating the NF-κB pathway and regulating the biological behavior of gastric cancer cells. Taken together, our study demonstrated that TRIM47 is involved in the proliferation and metastasis of gastric cancer through the CYLD/NF-κB pathway.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"106"},"PeriodicalIF":5.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614859","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":"N6-methyladenosine regulators in hepatocellular carcinoma: investigating the precise definition and clinical applications of biomarkers.","authors":"Xiaokai Yan, Yao Qi, Xinyue Yao, Lulu Yin, Hao Wang, Ji Fu, Guo Wan, Yanqun Gao, Nanjing Zhou, Xinxin Ye, Xiao Liu, Xing Chen","doi":"10.1186/s13062-024-00554-2","DOIUrl":"10.1186/s13062-024-00554-2","url":null,"abstract":"<p><strong>Background: </strong>Accurately identifying effective biomarkers and translating them into clinical practice have significant implications for improving clinical outcomes in hepatocellular carcinoma (HCC). In this study, our objective is to explore appropriate methods to improve the accuracy of biomarker identification and investigate their clinical value.</p><p><strong>Methods: </strong>Concentrating on the N6-methyladenosine (m6A) modification regulators, we utilized dozens of multi-omics HCC datasets to analyze the expression patterns and genetic features of m6A regulators. Through the integration of big data analysis with function experiments, we have redefined the biological roles of m6A regulators in HCC. Based on the key regulators, we constructed m6A risk models and explored their clinical value in estimating prognosis and guiding personalized therapy for HCC.</p><p><strong>Results: </strong>Most m6A regulators exhibit abnormal expression in HCC, and their expression is influenced by copy number variations (CNV) and DNA methylation. Large-scale data analysis has revealed the biological roles of many key m6A regulators, and these findings are well consistent with experimental results. The m6A risk models offer significant prognostic value. Moreover, they assist in reassessing the therapeutic potential of drugs such as sorafenib, gemcitabine, CTLA4 and PD1 blockers in HCC.</p><p><strong>Conclusions: </strong>Our findings suggest that the mutual validation of big data analysis and functional experiments may facilitate the precise identification and definition of biomarkers, and our m6A risk models may have the potential to guide personalized chemotherapy, targeted treatment, and immunotherapy decisions in HCC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"103"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602988","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":"ALKBH5 activates CEP55 transcription through m6A demethylation in FOXP2 mRNA and expedites cell cycle entry and EMT in ovarian cancer.","authors":"Junhui Yu, Xing Chen, Xiaoxiao Ding, Kang Lin, Tianxin Zhang, Kai Wang","doi":"10.1186/s13062-024-00551-5","DOIUrl":"10.1186/s13062-024-00551-5","url":null,"abstract":"<p><strong>Background: </strong>Centrosomal protein of 55 kDa (CEP55) overexpression has been linked to tumor stage, aggressiveness of the tumor, poor prognosis, and metastasis. This study aims to elucidate the action of CEP55 in ovarian cancer (OC) and the regulation by the alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5)/Forkhead box protein P2 (FOXP2) axis.</p><p><strong>Methods: </strong>Differentially expressed genes in OC were identified using in silico identification, followed by prognostic value assessment. Lentiviral vectors were constructed to downregulate CEP55 in OC cells, and colony formation, EdU, TUNEL, flow cytometry, Transwell assays, and Phalloidin staining were conducted. Transcription factors regulating CEP55 were predicted and verified, and rescue experiments were performed. The effect of ALKBH5-mediated demethylation on FOXP2 mRNA stability and OC cell cycle and EMT were analyzed.</p><p><strong>Results: </strong>High expression of CEP55 in OC was linked to unsatisfactory prognosis of patients. Knockdown of CEP55 repressed proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) while inducing apoptosis and cell cycle arrest in OC cells. FOXP2 bound to the promoter of CEP55 to repress CEP55 transcription. FOXP2 regulated transcriptional repression of CEP55 to impede the malignant progression of OC and inhibit tumor metastasis. ALKBH5-mediated demethylation modification induced mRNA degradation of FOXP2. Knockdown of ALKBH5 induced cell cycle arrest and inhibited EMT in OC cells.</p><p><strong>Conclusions: </strong>ALKBH5 hinders FOXP2-mediated transcriptional repression of CEP55 to promote the malignant progression of OC via cell cycle and EMT.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"105"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603021","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":"FXR1 associates with and degrades PDZK1IP1 and ATOH8 mRNAs and promotes esophageal cancer progression.","authors":"Faiz Ali Khan, Dalia Fouad, Farid S Ataya, Na Fang, Jingcheng Dong, Shaoping Ji","doi":"10.1186/s13062-024-00553-3","DOIUrl":"10.1186/s13062-024-00553-3","url":null,"abstract":"<p><strong>Background: </strong>The growing body of evidence suggests that RNA-binding proteins (RBPs) have an important function in cancer biology. This research characterizes the expression status of fragile X-related protein 1 (FXR1) in esophageal cancer (ESCA) cell lines and understands its mechanistic importance in ESCA tumor biology.</p><p><strong>Methods: </strong>The role of FXR1, PDZK1IP1, and ATOH8 in the malignant biological behaviors of ESCA cells was investigated using in-vitro and in-vivo experiments.</p><p><strong>Results: </strong>FXR1 was aberrantly overexpressed at both the transcript and protein levels in ESCA cells. Deficiency of FXR1 in ESCA cells was associated with decreased cell proliferation, viability and compromised cell migration compared to the control group. In addition, the inhibition of FXR1 leads to the promotion of apoptosis and cell cycle arrest in ESCA cells. Furthermore, FXR1 knockdown stabilizes senescence markers, promoting cellular senescence and decreasing cancer growth. Mechanistically, FXR1 negatively regulated PDZK1IP1 or ATOH8 transcripts by promoting mRNA degradation via direct interaction with its 3'UTR. PDZK1IP1 or ATOH8 overexpression predominantly inhibited the tumor-promotive phenotype in FXR1-overexpressed cells. Furthermore, FXR1 inhibition and PDZK1IP1 or ATOH8 overexpression in combination with FXR1-overexpressed cells significantly decreased xenograft tumor formation and enhanced nude mouse survival without causing apparent toxicity (P < 0.01). In the FXR1 knockdown group, the tumor weight of mice decreased by 80% compared to the control group (p < 0.01).</p><p><strong>Conclusions: </strong>Our results demonstrate FXR1's oncogenic involvement in ESCA cell lines, suggesting that FXR1 may be implicated in ESCA development by regulating the stability of PDZK1IP1 and ATOH8 mRNAs. For the first time, our findings emphasize the importance of FXR1-PDZK1IP1 and -ATOH8 functional modules in the development of ESCA, which might have potential diagnostic or therapeutic implications.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"104"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602986","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":"RNF19A inhibits bladder cancer progression by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway.","authors":"Hao Deng, Guanghai Ji, Jun Ma, Jun Cai, Shaoping Cheng, Fan Cheng","doi":"10.1186/s13062-024-00562-2","DOIUrl":"10.1186/s13062-024-00562-2","url":null,"abstract":"<p><strong>Background: </strong>The role of the RING finger protein superfamily in carcinogenesis has been widely studied, but one member of this family, RNF19A, has not yet been thoroughly explored in bladder cancer (BCa).</p><p><strong>Methods: </strong>The expression levels of RNF19A in BCa samples and cell lines were analysed through data mining of public resources and further experiments. BCa cells in which RNF19A was stably overexpressed or knocked down were generated through lentivirus infection. The effects of RNF19A on cell proliferation, migration, and invasion were explored by performing a series of in vitro experiments, including CCK-8, colony formation, wound healing, and Transwell invasion assays. Using bioinformatics methods and multiple experiments, including western blot, qRT‒PCR, immunoprecipitation, cycloheximide, ubiquitination, and rescue assays, the mechanism underlying the effect of RNF19A on the progression of BCa was investigated.</p><p><strong>Results: </strong>Here, we found that RNF19A expression was reduced in BCa samples and cell lines and that lower RNF19A expression predicted shorter overall survival of BCa patients. Functionally, forced expression of RNF19A suppressed BCa cell proliferation, migration, and invasion by inactivating the AKT/mTOR signalling pathway, whereas silencing RNF19A had the opposite effects. Mechanistically, RNF19A could directly interact with ILK and promote its ubiquitination and degradation. Rescue experiments revealed that forced ILK expression partially rescued the decreased phosphorylation of AKT, mTOR, and S6K1 caused by RNF19A overexpression and that the increased levels of the p-AKT, p-mTOR, and p-S6K1 proteins induced by RNF19A knockdown were eliminated after silencing ILK. Similarly, the effects of RNF19A overexpression or knockdown on the phenotypes of cell proliferation, migration, and invasion could also be restored by forced or decreased ILK expression.</p><p><strong>Conclusions: </strong>RNF19A suppressed the proliferation, migration, and invasion abilities of BCa cells by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway. RNF19A might be a potential prognostic biomarker and promising therapeutic target for BCa.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"102"},"PeriodicalIF":5.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589501","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":"Discovery of potential natural therapeutics targeting cell wall biosynthesis in multidrug-resistant Enterococcus faecalis: a computational perspective.","authors":"Km Rakhi, Monika Jain, Amit Kumar Singh, Mohd Sajid Ali, Hamad A Al-Lohedan, Jayaraman Muthukumaran","doi":"10.1186/s13062-024-00538-2","DOIUrl":"10.1186/s13062-024-00538-2","url":null,"abstract":"<p><strong>Background: </strong>Identifying therapeutic inhibitors of crucial enzymes involved in the peptidoglycan biosynthesis pathway is pivotal for developing new treatments against multidrug-resistant Enterococcus faecalis V583. MurM, an essential enzyme in this pathway, plays a significant role in the bacterium's cell wall synthesis, making it an attractive druggable target for novel antimicrobial strategies. This study explored the potential of natural compounds as inhibitors of MurM, aiming to discover promising drug candidates that could serve as the foundation for future therapeutic development.</p><p><strong>Methods: </strong>The three-dimensional structure of MurM was predicted, optimized, and its binding pocket was analyzed by comparing it with related structures. Over 4,70,000 natural compounds from the COCONUT database were subjected to virtual high-throughput screening (vHTS). The top lead candidates were selected based on their Lipinski's profile, ADME profile, toxicity profile, estimated binding free energy (ΔG) and estimated inhibition constant (Ki). Interaction pattern analysis was used to evaluate the non-covalent interactions between the inhibitors and key residues in MurM's binding pocket. Molecular dynamics simulations were performed over 300 ns to assess the structural stability and impact of these inhibitors on MurM's enzyme.</p><p><strong>Results: </strong>Three lead compounds-CNP0056520, CNP0126952, and CNP0248480-were identified and prioritized with estimated ΔG ranging from - 9.35 to -7.9 kcal/mol. Molecular dynamics simulations revealed minimal impact on MurM's overall structure and dynamics, with the candidate inhibitors forming stable protein-ligand complexes. These interactions were supported by several non-covalent interactions between the candidate inhibitors and key residues within MurM's binding pocket.</p><p><strong>Conclusion: </strong>These findings suggest that the identified natural product candidates could serve as promising inhibitors of MurM, potentially leading to novel therapeutics targeting cell wall biosynthesis in multidrug-resistant E. faecalis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"101"},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581283","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":"Characterization of gut microbiota dynamics in an Alzheimer's disease mouse model through clade-specific marker-based analysis of shotgun metagenomic data.","authors":"Francesco Favero, Angela Re, Mohammed Salim Dason, Teresa Gravina, Mara Gagliardi, Marta Mellai, Marco Corazzari, Davide Corà","doi":"10.1186/s13062-024-00541-7","DOIUrl":"10.1186/s13062-024-00541-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder significantly impairing cognitive faculties, memory, and physical abilities. To characterize the modulation of the gut microbiota in an in vivo AD model, we performed shotgun metagenomics sequencing on 3xTgAD mice at key time points (i.e., 2, 6, and 12 months) of AD progression. Fecal samples from both 3xTgAD and wild-type mice were collected, DNA extracted, and sequenced. Quantitative taxon abundance assessment using MetaPhlAn 4 ensured precise microbial community representation. The analysis focused on species-level genome bins (SGBs) including both known and unknown SGBs (kSGBs and uSGBs, respectively) and also comprised higher taxonomic categories such as family-level genome bins (FGBs), class-level genome bins (CGBs), and order-level genome bins (OGBs). Our bioinformatic results pinpointed the presence of extensive gut microbial diversity in AD mice and showed that the largest proportion of AD- and aging-associated microbiome changes in 3xTgAD mice concern SGBs that belong to the Bacteroidota and Firmicutes phyla, along with a large set of uncharacterized SGBs. Our findings emphasize the need for further advanced bioinformatic studies for accurate classification and functional analysis of these elusive microbial species in relation to their potential bridging role in the gut-brain axis and AD pathogenesis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"100"},"PeriodicalIF":5.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543712","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":"Disulfidptosis-related subtype and prognostic signature in prostate cancer.","authors":"Zhen Kang, Zheng-Hua Wan, Rui-Cheng Gao, Dong-Ning Chen, Qing-Shui Zheng, Xue-Yi Xue, Ning Xu, Yong Wei","doi":"10.1186/s13062-024-00544-4","DOIUrl":"10.1186/s13062-024-00544-4","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear.</p><p><strong>Methods: </strong>Firstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot.</p><p><strong>Results: </strong>Although SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients.</p><p><strong>Conclusion: </strong>This study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"97"},"PeriodicalIF":5.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495247","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}