Hereditas最新文献

{"title":"Identification of prognostic biomarker of non-small cell lung cancer based on mitochondrial permeability transition-driven necrosis-related genes and determination of anti-tumor effect of ARL14.","authors":"Zhifei Ma, Wen Chen, Aiping Zhang, Xiaokang Shen, Lin Zheng","doi":"10.1186/s41065-025-00379-7","DOIUrl":"10.1186/s41065-025-00379-7","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial permeability transition (MPT)-driven necrosis (MPTDN) is a non-apoptotic mode of cell death triggered by oxidative stress and cytosolic Ca²⁺ overload. Recent evidence suggests that activation of MPTND can effectively induce cancer cell death and may represent a novel therapeutic strategy for cancer. Yet, the role of MPTDN-related genes in non-small cell lung cancer (NSCLC) remains unrevealed. This study aimed to identify MPTDN-related biomarkers for predicting prognosis and guiding treatment in NSCLC.</p><p><strong>Methods: </strong>Gene expression profiles and clinical information of NSCLC were collected from public databases, and MPTDN-related genes were obtained from published article. Differential expressed MPTDN-related genes in NSCLC and control were screened, and molecular clusters were obtained. Based on the differentially expressed genes (DGEs) between clusters, univariate Cox and LASSO regression analyses were performed to screen biomarkers, followed by nomogram construction. Correlations between these biomarkers and immune cell infiltration, immune checkpoints, and chemotherapeutic agents were observed. Expression levels of MPTDN-related biomarkers were detected using RT-qPCR in NSCLC tissues and cells. Moreover, the biological function of ARL14 in NSLCL was verified in vitro.</p><p><strong>Results: </strong>Thirty-five differential MPTDN-related genes were identified, and two molecular clusters were obtained. Three biomarkers with prognostic values were finally screened, including ARL14, ZDHHC11B, and HLF. Among them, ARL14 was significantly upregulated in tumor samples, while ZDHHC11B and HLF were downregulated. Nomogram containing three genes exhibited predictive accuracy in 1, 3, and 5-year survival rates. Three gene were strongly associated with most immune cells, immune checkpoints, and drugs sensitivity. RT-qPCR confirmed that expression levels of three genes in tissues or cells were consistent with the results of bioinformatics analysis. Finally, ARL14 knockdown inhibited the malignant phenotype of NSCLC cells.</p><p><strong>Conclusion: </strong>We first performed the comprehensive analysis of MPTDN in NSCLC and screened three NSCLC-related biomarkers as promising biomarkers. ARL14 might be a new potential target for therapy of NSCLC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"16"},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance.","authors":"Senhui Wei, Ying Li, Jing Zhou, Yongming Xia","doi":"10.1186/s41065-025-00364-0","DOIUrl":"10.1186/s41065-025-00364-0","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) presents a significant global health burden, necessitating a deeper understanding of its molecular underpinnings for improved diagnostics and therapeutics.</p><p><strong>Methods: </strong>In this study, we investigated the expression profiles and clinical implications of MAP3K genes in GC using in silico and in vitro experiments.</p><p><strong>Results: </strong>Utilizing RT-qPCR analysis, we observed significant up-regulation of MAP3K1, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 in GC cell lines, while MAP3K2, MAP3K3, MAP3K11, MAP3K12, MAP3K13, MAP3K14, and MAP3K15 exhibited down-regulation. Prognostic evaluation revealed that elevated expression of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 was associated with shorter overall survival (OS), emphasizing their clinical significance. Furthermore, the diagnostic potential was demonstrated through robust Receiver operating characteristics (ROC) curve analysis, indicating the strong discriminatory power of these genes in distinguishing GC patients. Proteomic analysis further confirmed the higher expression of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 genes in GC. Methylation profiling further supported the idea that promoter hypomethylation of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 genes was associated with their up-regulation. Single-cell functional analysis elucidated the involvement of MAP3K genes in shaping the tumor microenvironment. miRNA-mRNA network analysis revealed intricate regulatory mechanisms, with hsa-mir-200b-3p emerging as a key regulator. Finally, the MAP3K1 knockdown has shown significant impacts on the cellular behavior of the BGC823 cells.</p><p><strong>Conclusion: </strong>This comprehensive assessment provides valuable insights into the role of MAP3K genes in GC, offering avenues for further research and therapeutic exploration.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"15"},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between chronic obstructive pulmonary disease and osteoporosis: Mendelian randomization combined with bibliometric analysis.","authors":"Fangjun Yang, Huaming Wang, Miaomiao Liu, Shengtai Pei, Xiaoming Qiu","doi":"10.1186/s41065-025-00373-z","DOIUrl":"10.1186/s41065-025-00373-z","url":null,"abstract":"<p><strong>Background: </strong>Previous observational studies have reported an association between chronic obstructive pulmonary disease (COPD) and osteoporosis (OP). The aim of this study is to investigate the causal relationship between COPD and OP by two-sample Mendelian randomization (MR) analysis. The current status of cross-sectional research between COPD and OP in the past decade was explored through bibliometrics.</p><p><strong>Methods: </strong>Single nucleotide polymorphisms (SNPs) that have been found to be strongly associated with COPD were used as instrumental variables (IVs) in MR Analysis. The primary outcome of the study was BMD measurement at five specific anatomical sites, namely the whole body, femoral neck, lumbar spine, forearm, and heel. These BMD measurements were derived primarily from a genome-wide association study (GWAS) and summary statistics from the International Genetic Factors Consortium for Osteoporosis (GEFOS). The main analysis method was inverse variance weighting (IVW). Multiple sensitivity analyses were performed to assess the robustness and reliability of the current MR Results. Further confirmatory MR Analysis between COPD and OP was applied. In bibliometrics. Publications were extracted from the Web of Science core collection publications related to osteoporosis and sarcopenia published between January 2014 and October 2024; Bibliometrics and visualization were performed by Microsoft Office Excel, Citespace, and R (Bibliometrix).</p><p><strong>Results: </strong>The MR Findings suggest that there is no causal relationship between COPD and BMD at five specific anatomical sites. The results of the primary IVW MR Analysis were generally supported by our sensitivity MR Analysis. We performed MR Analysis for the validation of COPD and OP (IVW OR: 1.019; 95%CI: 0.898-1.564; p = 0.768) also did not support a causal relationship between COPD and BMD. A total of 471 articles written by 1119 organizations from 42 countries/regions by 3331 authors and published in 238 journals were identified in the bibliometric analysis. China is the leading country in terms of the number of publications. China Medical University contributed the most publications. The International Journal of Chronic Obstructive Pulmonary Disease has the highest publication in this field.</p><p><strong>Conclusions: </strong>In conclusion, This MR Study found no causal relationship between COPD and OP, suggesting that the observed associations may be due to common genetic effects or environmental confounders. The global research trends in this field in the past decade were summarized through bibliometric analysis, and care became the focus of future research on the relationship between copd and OP.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"14"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomics-based investigation of its impact on the pathogenesis of coronary atherosclerosis: a Mendelian randomization study.","authors":"Qun Wang, Yuan Cao, Lianqun Jia","doi":"10.1186/s41065-025-00367-x","DOIUrl":"10.1186/s41065-025-00367-x","url":null,"abstract":"<p><strong>Background: </strong>Considerable attention has been devoted to investigating the association between lipid metabolites and cardiovascular diseases, particularly coronary atherosclerosis.</p><p><strong>Methods: </strong>A two-sample MR framework was used to investigate the relationship between lipid metabolites and the risk of coronary atherosclerosis. Two GWAS datasets were examined to take intersections of SNPs from 51,589 cases and 343,079 controls, and 14,334 cases and 346,860 controls to determine genetic susceptibility to coronary atherosclerosis. Random-effects inverse variance weighted (IVW) MR analyses were performed by a series of sensitivity assessments to measure the robustness of our findings and to detect any violations of MR assumptions.</p><p><strong>Results: </strong>Through IVW, MR-Egger and weighted median regression methods, we inferred that these six lipid metabolites: cholesterol levels, sterol ester (27:1/18:2) levels, triacylglycerol (52:4) levels, triacylglycerol (52:5) levels, diacylglycerol (18:1_18.2) levels, triacylglycerol (53:4), could directly impact the development of atherosclerosis.</p><p><strong>Conclusion: </strong>In conclusion, our study comprehensively illustrates a causal relationship between lipid metabolites and the risk of coronary atherosclerosis. Furthermore, cholesterol levels, sterol ester (27:1/18:2) levels, triacylglycerol (52:4) levels, triacylglycerol (52:5) levels, diacylglycerol (18:1_18.2) levels, and triacylglycerol (53:4) levels are positively correlated with the risk of coronary atherosclerosis. These six lipid metabolites have the potential as new predictors of the risk of atherosclerosis, providing new insights into the treatment and prevention of cardiovascular diseases.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"13"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediating Mendelian randomization in the proteome identified potential drug targets for obesity-related allergic asthma.","authors":"Jiannan Lin, Shuwen Lu, Xiaoyu Zhao","doi":"10.1186/s41065-025-00376-w","DOIUrl":"10.1186/s41065-025-00376-w","url":null,"abstract":"<p><strong>Background: </strong>With the development of the economy, the number of obese patients has been increasing annually worldwide. The proportion of asthma patients associated with obesity is also gradually rising. However, the pathogenesis of obesity-related asthma remains incompletely understood, and conventional pharmacological treatments generally show limited efficacy.</p><p><strong>Objective: </strong>This study aims to explore the causal relationship between obesity and allergic asthma, elucidate the pathogenesis of obesity-related asthma, and identify the plasma proteins involved in its development, providing new insights for clinical interventions.</p><p><strong>Methods: </strong>In this study, we employed a two-step approach for mediation Mendelian randomization (MR) analysis, utilizing stringent selection criteria to identify instrumental variables (IVs). This approach was used to assess the causal impact of obesity on allergic asthma and to validate the plasma proteins identified as mediating factors. We further explored the functions and enriched pathways of the mediating proteins using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, we conducted drug-targeted MR analysis to evaluate the potential of each mediator plasma proteins as a drug target gene. If significant heterogeneity remained among the IVs, we applied the weighted median method as the primary analytical tool. Otherwise, we utilized the inverse variance weighted (IVW) method as the main analytical approach. Additionally, we conducted various sensitivity analyses and statistical tests to further illustrate the robustness of the observed associations.</p><p><strong>Results: </strong>The research findings indicate a causal relationship between obesity and allergic asthma. Plasma proteins such as TPST1, ROR1, and DAPK1 mediate this relationship, with TPST1 accounting for over 10% of the mediation effect. GO and KEGG analyses show that the genes corresponding to these mediator proteins are primarily enriched in pathways related to responses to stimuli, carbohydrate synthesis and metabolism, regulation of certain protein activities, and synaptic connections. The drug-targeted MR analysis suggests that SIGLEC12, BOLA1, HOMER2, and TPST1 all have the potential to be drug target genes.</p><p><strong>Conclusion: </strong>This study suggests that obese patients defined by BMI may promote the development of allergic asthma by influencing the expression of plasma proteins such as TPST1, ROR1, and DAPK1. Furthermore, some of these plasma proteins, including TPST1, could potentially serve as therapeutic targets for treating allergic asthma in these patients. However, further research is needed to explore their therapeutic potential and the mechanisms underlying their effects.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"12"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 compound heterozygous mutation in the DYNC2H1 gene in a Chinese family with Jeune syndrome.","authors":"Sujie Xiong, Guangyao Hu, Yao Zhou, Fei Sun, Yanlin Ma","doi":"10.1186/s41065-025-00375-x","DOIUrl":"https://doi.org/10.1186/s41065-025-00375-x","url":null,"abstract":"<p><strong>Background: </strong>The dynein cytoplasmic two heavy chain 1 (DYNC2H1) gene encodes a cytoplasmic dynein subunit. Cytoplasmic dyneins transport cargo towards the minus end of microtubules and are thus termed the \"retrograde\" cellular motor. Mutations in DYNC2H1 are the main causative mutations of short rib-thoracic dysplasia syndrome type III with or without polydactyly (SRTD3). Early diagnosis of SRTD3 prenatally by ultrasound alone is difficult. In this case, a couple who gave birth to three consecutive babies with SRTD3 requested fertility guidance to avoid having another baby with SRTD3.</p><p><strong>Methods: </strong>Cytogenetic and molecular genetic analyses of amniotic fluid via whole-genome sequencing (WGS), routine G-banded karyotype analysis, fluorescent quantitative polymerase chain reaction, and whole-exome sequencing (WES) were performed at 19 weeks. Peripheral blood samples from the parents were also screened by Sanger sequencing for SRTD3-related mutations.</p><p><strong>Results: </strong>Two compound heterozygous mutations, c.10,594 C > T and c.7720G > A, in the DYNC2H1 gene were identified, which were inherited from the mother and father, respectively. The foetus's mother is heterozygous for the c.10,594 C > T variant, and the foetus's father is heterozygous for the c.7720G > A variant. The mutation c.10,594 C > T, which is a nonsense mutation believed to be pathogenic, has been previously reported. The mutation c.7720G > A, which is a missense mutation, has yet to be reported. Moreover, no chromosomal abnormalities or pathogenic copy number variations (CNVs) were detected in the foetus. The patient did not become pregnant after PGT-M and IVF-ET. This family subsequently accepted donated eggs; a successful pregnancy occurred, and a healthy girl was born.</p><p><strong>Conclusion: </strong>The compound heterogeneous mutations in DYNC2H1 ultimately accounts for the diversity of disease phenotypes reported in this study and can be used to guide future pregnancies. Our findings expand the mutation spectrum of DYNC2H1 in this rare disease and highlight the value of WES in the diagnosis of skeletal dysplasia with unclear prenatal indications.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"11"},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis.","authors":"Sheng Chen, Yangyong Luo, Simin Ruan, Guosen Su, Guoxing Huang","doi":"10.1186/s41065-025-00372-0","DOIUrl":"10.1186/s41065-025-00372-0","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC).</p><p><strong>Methods: </strong>The protein levels of CEP55 and ILF3 were detected by immunoblotting or immunohistochemistry, and their mRNA levels were assessed by quantitative PCR. Cell invasion and migration were evaluated by transwell assay. Cell apoptosis and colony formation were tested by flow cytometry and colony formation assays, respectively. RNA immunoprecipitation (RIP) experiment and CEP55 mRNA stability assay were used to validate the relationship between ILF3 and CEP55 mRNA. Subcutaneous xenograft studies were performed to analyze the role of ILF3 depletion in tumor growth.</p><p><strong>Results: </strong>CEP55 and ILF3 were upregulated in most of human BC samples and MDA-MB-231 and MCF-7 BC cells. The depletion of CEP55 or ILF3 impaired the growth, invasion, and migration of MDA-MB-231 and MCF-7 cells, while promoted their ferroptosis and apoptosis. Mechanistically, ILF3 stabilized CEP55 mRNA to regulate CEP55 expression in BC cells. CEP55 restoration partially rescued the malignant potential defects of ILF3-depleted BC cells and attenuates their ferroptosis. Moreover, ILF3 depletion enhanced the anti-tumor growth activity of the ferroptosis inducer erastin in MDA-MB-231 subcutaneous xenograft tumors.</p><p><strong>Conclusion: </strong>Our observations indicate that the depletion of ILF3 impairs the malignant potential of BC cells and promotes their ferroptosis by downregulating CEP55 expression. Silencing ILF3 or CEP55 could represent a potential therapeutic strategy for BC treatment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"10"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis.","authors":"Yuhang Xing, Rui Pu, Mengdie Fu, Zhikang Wang, Zhen Wang, Xiaopeng Shang, Guoli Yang, Zhiwei Jiang","doi":"10.1186/s41065-025-00370-2","DOIUrl":"10.1186/s41065-025-00370-2","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies have confirmed the relationship between personality trait neuroticism and physical health. However, the relationship between neuroticism and frailty remains unconfirmed. This study employed a bi-directional two-sample Mendelian randomization (MR) approach to investigate the causal relationship between neuroticism and frailty.</p><p><strong>Methods: </strong>The neuroticism genome-wide association study (GWAS) data from the UK Biobank contained twelve neuroticism-related traits with 489,212 participants. The genetic frailty index data were extracted from the UK Biobank and Swedish TwinGene, involving 175,226 individuals. Independent genetic variants associated with neuroticism and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and MR-PRESSO were mainly used for MR analysis.</p><p><strong>Results: </strong>The MR analysis showed a positive causal relationship between neuroticism and the risk of frailty (odds ratio (OR) = 1.627, 95% confidence interval (CI) = 1.538-1.722, P < 0.001). In the reverse direction, frailty had a causal effect on a higher risk of neuroticism (OR = 1.270, 95% CI = 1.173-1.375, P < 0.001). Steiger tests indicated that reverse causation did not bias the identified causal relationships.</p><p><strong>Conclusions: </strong>Our study provides genetic evidence suggesting a bi-directional causal relationship between frailty and neuroticism. In this bi-directional MR study, there were positive causal relationships between neuroticism-related phenotypes and frailty, and in the reverse direction, frailty was also positively correlated with neuroticism.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"8"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-dependent DLG2 inhibits the malignant progression of cervical cancer by inactivating the Hippo/YAP signaling.","authors":"Mei Pu, Xia Xiao, Shasha Lv, Daqing Ran, Qian Huang, Mingming Zhou, Qirong Lei, Lingshuang Kong, Qing Zhang","doi":"10.1186/s41065-025-00365-z","DOIUrl":"10.1186/s41065-025-00365-z","url":null,"abstract":"<p><strong>Background: </strong>Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer and its clinical implications.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction and western blotting assays were employed to detect RNA and protein expression, respectively. Colony formation assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, and transwell assays were conducted for cell functional analysis. A xenograft mouse model assay was performed to analyze tumor tumorigenesis in vivo. m6A RNA immunoprecipitation assay was used to analyze the association of METTL3 and DLG2.</p><p><strong>Results: </strong>DLG2 was underexpressed in cervical cancer tissues and cells. Elevating DLG2 levels significantly suppressed cervical cancer cell proliferation, migration, and invasion, while promoting apoptosis. Additionally, DLG2 overexpression led to the deactivation of the Hippo/YAP signaling pathway. In vivo, DLG2 overexpression was shown to reduce tumor formation. We also discovered that METTL3 destabilized DLG2 mRNA through an m6A-dependent mechanism. Moreover, lowering DLG2 expression mitigated the effects of METTL3 silencing on cervical cancer cell malignancy.</p><p><strong>Conclusion: </strong>DLG2 acted as a tumor suppressor in cervical cancer by inhibiting the Hippo/YAP signaling pathway. The METTL3-dependent regulation of DLG2 mRNA stability could be a critical factor in cervical cancer progression.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"9"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal association among smoking, bitter beverage consumption, and risk of osteoporosis: a two-sample mendelian randomization-based study.","authors":"Yanqian Wu, Jianqian Chao, Min Bao, Na Zhang, Leixia Wang","doi":"10.1186/s41065-025-00371-1","DOIUrl":"10.1186/s41065-025-00371-1","url":null,"abstract":"<p><strong>Objectives: </strong>Two-sample MR methods were employed to analyze the impact of smoking and bitter beverage consumption on the risk of osteoporosis and osteoporosis with pathological fractures, in order to assess the causal association.</p><p><strong>Methods: </strong>Publicly available genome-wide association study summary data were analyzed using MR methods. The exposures investigated were smoking (smoking per day, smoking initiation, and lifetime smoking index) and bitter beverages (coffee, tea, bitter alcoholic beverages, bitter non-alcoholic beverages, and total bitter beverages). The outcomes examined were the risk of osteoporosis and osteoporosis with pathological fractures. The inverse-variance weighted (IVW) method was used as the main statistical model. The stability and reliability of the results were verified by the Cochran's Q test, the Egger-intercept test, and the leave-one-out analysis.</p><p><strong>Results: </strong>Smoking per day was causally associated with the risk of osteoporosis OR = 1.417, 95% CI = 1.119-1.794, P = 0.003), and lifetime smoking index had a possible genetic causal association with the risk of osteoporosis with pathological fractures (OR = 4.187, 95% CI = 1.909-9.184, P < 0.001). No genetic causal association was found between smoking initiation or lifetime smoking index and the risk of osteoporosis (P > 0.05). No genetic causal association was identified between smoking per day or smoking initiation and the risk of osteoporosis with pathological fractures (P > 0.05). Total and bitter non-alcoholic beverage consumption showed a potential effect on the risk of osteoporosis (OR = 3.687, 95% CI = 1.535-8.858, P = 0.003 and OR = 3.040, 95% CI = 1.466-6.304, P = 0.002, respectively).</p><p><strong>Conclusions: </strong>This study found smoking raises the risk of osteoporosis and osteoporosis with pathological fractures based on genetics. Certain bitter beverages are linked to an increased osteoporosis risk.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"7"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}