Biochemical Genetics最新文献

{"title":"LncIMF1 Promotes Adipogenesis of Porcine Intramuscular Preadipocyte by Sponging miR-187.","authors":"Ming Feng, Xudong Yi, Ziyi Zhang, Jiahua Zhu, He Yu, Lianxi Ming, Weijun Pang","doi":"10.1007/s10528-025-11061-y","DOIUrl":"https://doi.org/10.1007/s10528-025-11061-y","url":null,"abstract":"<p><p>Intramuscular fat, which is closely related to the traits of tenderness, juiciness, and flavor of pork, is regulated by numerous molecular regulatory mechanisms that have been regarded as an important agricultural research area. Long noncoding RNAs (lncRNAs) are emerging regulators involved in adipogenesis due to their functional diversity. In this study, we identified a novel lncRNA related to porcine adipogenesis, named lncIMF1, based on previous RNA sequencing results. Our results suggested that lncIMF1 was most abundantly expressed in adipose tissue and located in both the cytoplasm and nucleus. Besides, lncIMF1 promoted the proliferation and differentiation, while inhibited apoptosis of intramuscular preadipocytes. Moreover, lncIMF1 could act as a molecular sponge for miR-187, inhibiting the binding of miR-187 and SMAD1, thereby promoting the expression of SMAD1 and enhancing the adipogenic differentiation of intramuscular preadipocytes. Additionally, we found that lncIMF1-miR187-SMAD1 axis could activate the p38-mitogen-activated protein kinase (MAPK) pathway. Taken together, our study provided new insights into the role of lncRNAs in the regulation of pork quality.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-526b-5p Regulates the Sensitivity of Colorectal Cancer to 5-Fluorouracil by Targeting TP53 in Organoid Models.","authors":"Lizhe Huang, Cun Liao, Zuming Xiong, Zhongyang Chen, Sen Zhang","doi":"10.1007/s10528-025-11045-y","DOIUrl":"https://doi.org/10.1007/s10528-025-11045-y","url":null,"abstract":"<p><p>This study aimed to explore the mechanisms through which microRNAs (miRNAs) regulate 5-fluorouracil (5-FU) sensitivity in colorectal cancer (CRC) using organoid models. Fresh tissue samples from CRC tumors were collected, and CRC organoids were isolated and cultured. The consistency between CRC organoids and their derived tissues was validated. CRC organoids were treated with 5-FU, and ATP activity was measured. High-throughput sequencing of CRC organoids, combined with Gene Expression Omnibus (GEO) data analysis, was performed to examine miRNA expression following 5-FU treatment. Next, we investigated the cellular function of miR-526b-5p in CRC organoids and cells. Dual-luciferase reporter assays validated the binding of miR-526b-5p to the 3' UTR of TP53 mRNA. We successfully established CRC organoids that exhibited characteristics consistent with their source tissues. 5-FU treatment suppressed the proliferation and ATP activity of CRC organoids. High-throughput sequencing of CRC organoids, combined with GEO data analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation, revealed that hsa-miR-526b-5p levels were elevated following 5-FU treatment in CRC organoids and cells. Furthermore, hsa-miR-526b-5p was upregulated in CRC tissues compared to adjacent normal tissues, correlating with poor survival in CRC patients. Overexpression of hsa-miR-526b-5p mitigated the inhibitory effects of 5-FU on CRC organoid proliferation, migration, invasion, and ferroptosis. In contrast, silencing of hsa-miR-526b-5p impaired cell function and ferroptosis. Additionally, overexpression of hsa-miR-526b-5p decreased TP53 mRNA and protein levels while increasing the expression of SLC7A11 mRNA and protein. Silencing of hsa-miR-526b-5p resulted in the opposite effect. hsa-miR-526b-5p directly targeted and inhibited TP53 expression. Overexpression of TP53 diminished the promotive effect of hsa-miR-526b-5p on ferroptosis-related proteins GPX4 and SLC7A11, whereas inhibition of TP53 reversed the impact of hsa-miR-526b-5p silencing. Our study demonstrates that hsa-miR-526b-5p targets TP53 to regulate 5-FU sensitivity in CRC through the ferroptosis pathway based on CRC organoid models.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Yield & Quality Potential of Peppermint (M. piperita L.) for the Study of Genetic Variability Through Induced Mutagenesis.","authors":"Akancha Gupta, Nashra Aftab, Priyanka Prasad, Himanshu Kumar Kushwaha, Puja Kumari, Ram Kishor, Vagmi Singh, Shivani Chandra, Anju Kumari Yadav, Birendra Kumar","doi":"10.1007/s10528-025-11028-z","DOIUrl":"https://doi.org/10.1007/s10528-025-11028-z","url":null,"abstract":"<p><p>Mentha piperita L. commonly known as peppermint, is valued for its essential oil, which is rich in menthol and has various applications. However, challenges such as low oil yield and poor oil quality have limited the potential of peppermint cultivation. This study aimed to develop a noble mutant of Mentha piperita that complements US-type peppermint oil, characterized by higher oil yield and improved oil quality, specifically targeting a menthol content of 36-46% and less than 5% menthofuran. Induced mutagenesis was achieved through gamma radiation, with seeds from a menthofuran-rich variety CIM-Indus of Mentha piperita subjected to varying doses (10 Gy, 20 Gy, 30 Gy, 40 Gy, 50 Gy, 70 Gy, 90 Gy, and 110 Gy). A broad range of diversity was observed among the resulting mutant lines, leading to the selection of improved lines. Notably, CIM-I452 exhibited the highest oil yield along with substantial herb yield, followed by CIM-I332 and CIM-I324. Lines CIM-I43, CIM-I44, CIM-I451, CIM-I32, CIM-I34, CIM-I332, and CIM-I452 were identified as menthol-rich, while CIM-I311 and CIM-I431 were menthofuran-rich. Additionally, CIM-I322 and CIM-I331 were recognized as limonene-rich lines. Because of the high menthol content and low amount of menthofuran, the mutant lines CIM-I452, CIM-I332, and CIM-I324 showed widely acceptance peppermint oil quality. These selected mutant lines exhibit promising mutant lines that may be utilised as parent lines for upcoming recombinant breeding or hybridization initiatives.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress-Related KEAP1 and NRF2 Genes Contributed to the Risk of Epithelial Ovarian Cancer.","authors":"Xiaoqian Tong, Xiaoli Zhu, Xila Wang, Yanlin Xu, Pei Huang, Leiqing Zhou, Yanxiang Ji, Lifang Wu","doi":"10.1007/s10528-025-11044-z","DOIUrl":"https://doi.org/10.1007/s10528-025-11044-z","url":null,"abstract":"<p><p>The NRF2/KEAP1 signaling pathway, crucial for cellular defense against oxidative stress, may influence epithelial ovarian cancer (EOC) risk. This study investigates the association between KEAP1 gene polymorphisms and EOC risk in Han Chinese individuals, while exploring correlations between these genetic variants and serum levels of KEAP1 and NRF2 proteins. We conducted a case-control study involving 1962 EOC patients and 2057 controls, genotyping ten tag single-nucleotide polymorphisms (SNPs) in KEAP1. Serum KEAP1 and NRF2 levels were measured using ELISA. Genetic association analyses and ANOVA were employed to assess relationships between SNPs, EOC risk, and serum protein levels. Notably, only SNP rs3177696 in KEAP1 showed a significant association with EOC risk. The G allele of rs3177696 conferred a protective effect against EOC (OR [95% CI] = 0.58 [0.47-0.72], P = 2.91 × 10^-7). Furthermore, rs3177696 genotypes were significantly associated with serum levels of both KEAP1 and NRF2, as well as their ratio. EOC patients carrying GG, AG, and AA genotypes exhibited mean serum KEAP1 levels of 2.46, 2.16, and 2.04 (P = 2.43 × 10^-9), respectively. Conversely, serum NRF2 levels decreased with increasing G allele copies (GG: 4.58, AG: 4.95, AA: 5.02; P = 0.0002). This study provides compelling evidence linking EOC risk to the oxidative stress-related gene KEAP1, with the G allele of rs3177696 demonstrating a protective effect. These findings suggest a potential role for the NRF2/KEAP1 pathway in EOC pathogenesis and highlight promising avenues for future research in EOC prevention and treatment strategies.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Curcumin in the Treatment of Intrauterine Adhesions Based on Network Pharmacology, Molecular docking, and Experimental Validation.","authors":"Qiaoxia Li, Yongyan Zhang, Haoyu Shen, Ziqian Wang, Jiezhuang Huang, Shuli Tang, Peiyue Chen, Zhifu Zhi","doi":"10.1007/s10528-025-11049-8","DOIUrl":"https://doi.org/10.1007/s10528-025-11049-8","url":null,"abstract":"<p><p>Intrauterine adhesions (IUA) is one of the most prevalent gynecological conditions affecting women of childbearing age. The active ingredient curcumin (CUR), derived from turmeric, is a promising candidate for the treatment of IUA. Nevertheless, the mechanism of action remains undetermined. This study investigates the role and mechanism of CUR in the treatment of IUA through network pharmacology, molecular docking, and molecular biology experiments. IUA-related targets were sourced from the GeneCards database. CUR-related targets were obtained from Herb and SwissTarget Prediction. Cytoscape version 3.10.2 was employed to construct PPI networks and to identify core targets. GO and KEGG enrichment analyses were conducted using the DAVID database. Additionally, molecular docking was employed to evaluate the interaction between CUR and core targets. Finally, the mechanism and targets of CUR in IUA were validated through animal experiments. A total of 122 common target points for CUR and IUA were identified. Topological analysis and KEGG analysis identified 20 core target points, encompassing multiple pathways, including inflammation and the PI3K/AKT signaling pathway. Molecular docking results demonstrated that CUR exhibits a strong binding affinity for the core target points. In vivo experiments indicate that CUR significantly alleviates the fibrosis and epithelial-mesenchymal transition (EMT) processes of the endometrium in IUA rats while inhibiting the overexpression of TGF-β1 in the uterine tissue of IUA rats and the activation of the PI3K/AKT and TLR4/NLRP3 signaling pathways. CUR can inhibit fibrosis and the EMT process in the endometrium of IUA rats, and its mechanism may be associated with the inhibition of the PI3K/AKT and TLR4/NLRP3 signaling pathways.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino Acid Metabolism-Related Gene Kynureninase (KYNU) as a Prognostic Predictor and Regulator of Diffuse Large B-Cell Lymphoma.","authors":"Yu Zhang, Shi Feng, Liemei Lv, Cong Wang, Ran Kong, Guangcai Zhong, Na Wang, Peipei Li, Xiangxiang Zhou","doi":"10.1007/s10528-025-11047-w","DOIUrl":"https://doi.org/10.1007/s10528-025-11047-w","url":null,"abstract":"<p><p>Dysregulation of amino acid metabolism is recognized to have a substantial influence on tumorigenesis and the modulation of tumor microenvironment. However, the role of amino acid metabolism-related genes in diffuse large B-cell lymphoma (DLBCL) remains undefined. Therefore, we aimed to explore the influence of amino acid metabolism-related genes in DLBCL using bioinformatics approaches. Consensus clustering demonstrated that the reprogramming of amino acid metabolism has prognostic value in DLBCL. Subsequently, we developed a risk model using LASSO-Cox regression analysis to accurately predict DLBCL prognosis and identified kynureninase (KYNU) as a potentially valuable biomarker. Analysis of immune infiltration was conducted to examine the correlation between risk scores and immune profiles. Furthermore, RT-qPCR showed that the KYNU mRNA levels were upregulated in OCI-LY1, OCI-LY3, and OCI-LY10 DLBCL cells compared with normal CD19+B lymphocytes. Cell proliferation assays and flow cytometry analysis showed that inhibition of KYNU expression reduced cell proliferation and induced apoptosis of DLBCL cells. Overall, we demonstrated the significant impact of amino acid metabolism on DLBCL. Our findings may help improve the assessment of disease prognosis and provide potential therapeutic strategies for DLBCL.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring miR-34a, miR-449, and ADAM2/ADAM7 Expressions as Potential Biomarkers in Male Infertility: A Combined In Silico and Experimental Approach.","authors":"Fariba Ghodrati, Kazem Parivar, Iraj Amiri, Nasim Hayati Roodbari","doi":"10.1007/s10528-025-11050-1","DOIUrl":"https://doi.org/10.1007/s10528-025-11050-1","url":null,"abstract":"<p><p>miR-34a and miR-449 are key miRNAs involved in sperm function and male fertility, with their dysregulation potentially contributing to male infertility. ADAM proteins, specifically ADAM2 and ADAM7, are also implicated in sperm function. This study investigates the interactions between miR-34a, miR-449, and ADAM2/ADAM7, exploring their roles in male infertility through both experimental analyses and molecular docking. In this case-control study, 15 infertile males and 15 healthy controls were included. Gene expression levels of miR-34a, miR-449, and SOX30 were measured using real-time PCR, while protein levels of ADAM7 and ADAM2 in sperm were assessed through western blotting. Additionally, molecular docking was performed to analyze the binding affinities between miR-34a/miR-449 and ADAM2/ADAM7, with docking scores and confidence levels evaluated. Expression levels of ADAM7 and ADAM2 proteins in sperm from the infertile group showed significant differences compared with the control group (P ≤ 0.05). A significant difference was observed in the expression of miR-449, miR-34a, and SOX30 genes between the control and infertile groups (P < 0.05). A significant correlation between miR-34a expression, ADAM7 protein expression, and sperm morphology was observed. However, no statistically significant correlation was found between miR-34a expression and sperm motility, sperm count, blastocyst, or embryo rates in ICSI and IVF (P ≥ 0.05). Molecular docking and dynamics studies revealed strong interactions between miR-34a/miR-449 and ADAM proteins. The ADAM7/miR-34a complex showed the highest binding affinity with a docking score of - 372.40 and a confidence score of 0.9884, followed by ADAM7/miR-449. Hydrogen bond analysis indicated stable binding, with 9 bonds for ADAM2/miR-34a and 7 for ADAM7/miR-34a. These interactions suggest a significant role in regulating sperm morphology and function.miR-34a, miR-449, ADAM7, and ADAM2 protein expression appear to be involved in the molecular mechanisms of male infertility. These parameters show potential as biomarkers in assisted reproductive technology techniques, particularly by influencing sperm morphology and function.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between ERBB2 and ERBB3 Polymorphisms and Dyslipidaemia and Serum Lipid Levels in a Chinese Population.","authors":"Lijun Zhu, Zhengmei Fang, Mengyun Huang, Lianping He, Miao Xu, Yue Yu, Yuelong Jin, Yan Chen, Yingshui Yao","doi":"10.1007/s10528-025-11048-9","DOIUrl":"https://doi.org/10.1007/s10528-025-11048-9","url":null,"abstract":"<p><p>Dyslipidaemia, characterised by abnormal lipid levels in the blood, is an important risk factor for cardiovascular disease. In this case-control study, the association between single-nucleotide polymorphisms in ERBB2 and ERBB3 genes and the risk of dyslipidaemia in a population from Northern Anhui, China was evaluated. Particularly, we analysed samples from 543 patients with dyslipidaemia and 648 healthy controls for five potentially functional polymorphisms using TaqMan assays. Multivariate logistic regression was used to assess the relationship between genotype and dyslipidaemia, adjusting for confounding variables. The ERBB2 rs2517955 and rs1058808 single-nucleotide polymorphisms were significantly associated with dyslipidaemia. The rs2517955 variant showed a protective effect against dyslipidaemia in males, individuals aged 55 years or younger, and those without diabetes. Similarly, the rs1058808 variant decreased the risk of dyslipidaemia in these stratified groups. Conversely, ERBB3 rs2292238 was associated with an increased risk of dyslipidaemia in patients with diabetes. Compared with the corresponding wild-type alleles, variant alleles of rs2517955 and rs1058808 were associated with a reduced risk of decreased high-density lipoprotein cholesterol levels. Additionally, ERBB2 rs2517955 variants were significantly linked to total cholesterol levels, whereas ERBB3 rs3741499 and rs877636 variants were significantly associated with low-density lipoprotein cholesterol levels. Our findings suggest that ERBB2 and ERBB3 polymorphisms are closely associated with the risk of dyslipidaemia in the Chinese population. These results provide valuable insights for further genetic studies of dyslipidaemia and the identification of potential therapeutic targets.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Molecular Spectrum of Wilson Disease in the Arab World: A Systematic Review","authors":"Halima Benzine,&nbsp;Saida Lhousni,&nbsp;Maria Rkain,&nbsp;Meryem Ouarzane,&nbsp;Redouane Boulouiz,&nbsp;Mohammed Bellaoui,&nbsp;Majida Charif","doi":"10.1007/s10528-025-11042-1","DOIUrl":"10.1007/s10528-025-11042-1","url":null,"abstract":"<div><p>Wilson disease is a rare monogenic disease characterized by copper overload in various organs, mainly the liver, the brain and the eyes. It has a prevalence ranging between 1/30,000 and 1/50,000, and it is caused by pathogenic variants in the <i>ATP7B</i> gene, which encodes a copper-transporting ATPase essential for regulating liver copper levels by directing copper to the secretory pathway and exporting excess copper into bile. It is a fatal disease if left untreated; however early diagnosis and effective treatment enable patient’s outcome improvement. Unfortunately, in the Arab world there is no collective data on Wilson disease. This systematic review presents an explicit overview on the clinical and molecular spectrum of Wilson disease in the Arab world. A literature search was conducted on five databases from their inception until April 2024, using a combination of words related to the genetics of Wilson disease in the Arab world. The search resulted in 48 relevant studies carried out in 13 Arab countries, in which 802 Wilson disease patients were reported, with a high rate of consanguinity, and a slight male predominance. Hepatic presentations were the most frequent features in patients, and a total of 92 variants were identified with a detection rate of 61.2%. Genotype–phenotype correlations were not established for the majority of variants. This review revealed a clinical and molecular heterogeneity of Wilson disease in the Arab world. Efforts from health authorities, clinicians and geneticists are recommended to improve diagnosis, reduce disease incidence and give more insights into the present-day understanding of Wilson disease in the Arab world.</p></div>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":"63 2","pages":"1198 - 1218"},"PeriodicalIF":2.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2 Knockdown Promotes the Ferroptosis of Colorectal Cancer Cells Via m5C Modification of SLC7A11 mRNA.","authors":"Ruibing Tong, Yuefeng Li, Junli Wang, Chengyu Liu, Yan Liu, Rongshuang Li, Xinghong Wang","doi":"10.1007/s10528-025-11035-0","DOIUrl":"https://doi.org/10.1007/s10528-025-11035-0","url":null,"abstract":"<p><p>The high occurrence and death rates of colorectal cancer (CRC) make it a major health concern. Recent studies have identified NOP2/Sun RNA methyltransferase family member 2 (NSUN2), an RNA methyltransferase, as a key regulator in various tumor types. However, how exactly NSUN2-mediated m5C alteration affects CRC is still a mystery. This study seeks to understand how NSUN2 contributes to the growth and death of colorectal cancer cells. New tissue samples were taken in order to investigate NSUN2 expression in CRC. In vitro tests were performed to evaluate NSUN2's function. We used m5C-methylated-RNA immunoprecipitation and RNA stability experiments to find out how NSUN2 works on Solute carrier family 7 member 11 (SLC7A11, also called xCT). Downregulation of NSUN2 limits CRC cell growth and induces ferroptosis, as we show that NSUN2 was substantially expressed in CRC. In terms of the molecular mechanism, NSUN2 controls the translation and stability of SLC7A11 mRNA by regulating its m5C methylation. Functional tests show that SLC7A11 compensates for the NSUN2 knockdown-induced decrease in cell proliferation. Additionally, SLC7A11 overexpression restores ferroptosis to CRC cells after NSUN2 knockdown. These findings emphasize NSUN2's crucial role in modulating colorectal cancer cell growth and survival via SLC7A11, pointing to promising new therapeutic targets.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}