Biochemical Genetics最新文献

{"title":"Complex Interplay of Tandem, Segmental, Whole Genome Duplication, and Re-organization Drives Expansion of SAUR Gene Family in Brassicaceae.","authors":"Richa Shukla, Ekta Pokhriyal, Sandip Das","doi":"10.1007/s10528-025-11167-3","DOIUrl":"https://doi.org/10.1007/s10528-025-11167-3","url":null,"abstract":"<p><p>Members of the SAUR, small auxin upregulated RNA, gene family initially identified as auxin inducible, mediate diverse developmental and adaptive processes in plants. Inspite of their importance, identification and analysis of homologs from Brassica juncea, a major oilseed crop, is lacking. Additionally, investigations into organisational complexity and evolutionary past across Brassicaceae remain to be investigated. The present study was therefore designed to identify members of the SAUR gene family in B. juncea, reconstruct phylogenetic relationship, and analyse the history of expansion of the SAUR gene family across Brassicaceae. Genome-wide in-silico analysis allowed us to identify 237 SAUR genes in the allotetraploid B. juncea (AABB genome), which are distributed in a clustered manner among all 18 chromosomes of the B. juncea genome. Comparative analysis with the diploid parents- B. rapa (AA) and B. nigra (BB) revealed conserved organisation pattern. A striking feature of SAUR genes is intronless nature of most members. Comparative analysis revealed ten clusters of tandemly arrayed genes (TAGs) in Arabidopsis thaliana; two of these clusters were lost, and 33 clusters that are orthologous to the rest of A. thaliana clusters were identified from B. juncea genome. Organisational complexity revealed the presence of putative bidirectional promoters between some SAUR genes. Phylogenetic reconstruction shows several SAUR genes of A. thaliana and B. juncea forming separate clades, indicating lineage-specific expansion. Inclusion of homologs from across Brassicaceae allowed us to perform comparative synteny analysis and hypothesize local duplications being responsible for the tandem organisation, and segmental duplications as driving mechanism for large-scale expansion. The present study allowed us to catalog homologs of the SAUR gene family in B. juncea. This study thus forms the foundation for functional characterization involving transcriptional regulation, generation, and analysis of reverse genetic models toward understanding their role in plant growth and development.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537651","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":"Functional Analysis of a Novel Missense Mutation c.1039A > G of TUBB8 in Infertile Women.","authors":"Min Guo, Fangfang Li, Lingyan Ren, Guiqin You, Ying Zhang, Juan Liu, Shengwen Huang","doi":"10.1007/s10528-025-11152-w","DOIUrl":"https://doi.org/10.1007/s10528-025-11152-w","url":null,"abstract":"<p><p>The TUBB8 gene is highly conserved in primates, and pathogenic mutations in this gene have been linked to defects in oocyte maturation, leading to infertility in women. This study aimed to identify a mutation in the TUBB8 gene in a family with female infertility and functionally validate the identified mutation to confirm its pathogenicity. Genomic DNA was extracted from the proband's peripheral blood for whole exome sequencing. DNA from the proband's parents was obtained for Sanger sequencing to trace the origin of the proband's mutation. Bioinformatics analysis, conservation analysis, and three-dimensional protein structure prediction were performed on the sequencing results. Wild-type and mutant TUBB8 expression plasmids for the identified mutation sites were constructed and transfected into HEK293T and HeLa cells. Changes in protein structure and gene expression were then assessed. The analysis revealed that the proband carried the TUBB8 mutation c.1039A > G, also present in her father and aunt. This mutation was classified as a Variant of Uncertain Significance (VUS). Protein structure prediction suggested that the TUBB8 p.N347D (c.1039A > G) mutant protein had an additional hydrogen bond compared to the wild-type protein. Still, no significant structural changes were observed in the three-dimensional model. Immunofluorescence staining showed that the TUBB8 c.1039A > G mutation did not disrupt cellular microtubule structure. In vitro assays indicated that the c.1039A > G mutation decreased mRNA and protein expression levels of TUBB8. This study describes a case of female infertility associated with a newly discovered heterozygous c.1039A > G mutation in the TUBB8 gene, which may reduce TUBB8 expression. These findings contribute to the genetic understanding and diagnosis of TUBB8-related diseases.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537656","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":"Generation of Leucine-Rich Repeat Kinase 2 (LRRK2) Knockout Neuroblastoma Cells SH-SY5Y by CRISPR/Cas9-Mediated Genome Editing.","authors":"Hui-Lan Jong, Kit-San Yuen, Dong-Yan Jin, Susan Ling Ling Hoe, Aini Ideris, Chee-Hong Tan, Sau-Kuen Lam, Yang-Mooi Lim, Soon-Keng Cheong","doi":"10.1007/s10528-025-11174-4","DOIUrl":"https://doi.org/10.1007/s10528-025-11174-4","url":null,"abstract":"<p><p>Leucine-rich repeat kinase 2 (LRRK2) is associated with Parkinson's disease, despite its low expression in the brain. Pathogenic mutations in LRRK2 enhance kinase activity and contribute to the disease's pathogenesis. Neuroblastoma SH-SY5Y cells, which also exhibit low LRRK2 expression, are extensively used as a model for Parkinson's disease. While less prominent, low-expression genes can play crucial roles in cellular processes, development, and disease. Knocking out such genes poses specific challenges, including difficulties in detection, incomplete knockout, and compensatory mechanisms that can obscure phenotypic changes. This study develops a strategy to knockout low-expression LRRK2 in SH-SY5Y cells effectively. Our approach employs a double-cut and multiple guide RNAs strategy, optimized electroporation parameters to enhance CRISPR/Cas9 plasmid delivery, refined clonal expansion technique, and a sensitive protein detection protocol. We successfully generate LRRK2 knockout SH-SY5Y cells using CRISPR/Cas9, with the knockout efficiency validated by PCR analysis, sequencing, and Western blot analysis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537657","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":"Silencing THBS1 in M2 Macrophages Exerts an Inhibitory Effect on Tongue Squamous Cell Carcinoma by Suppressing TGF-β Pathway.","authors":"Jia-Yu Liu, Yi-Yang Chen, Zhi-Yuan Lu, Li-Li Chen","doi":"10.1007/s10528-025-11179-z","DOIUrl":"https://doi.org/10.1007/s10528-025-11179-z","url":null,"abstract":"<p><p>Tongue squamous cell carcinoma (TSCC) is a common oral and maxillofacial malignancy. Thrombospondin-1 (THBS1), acting in the extracellular matrix, impacts cell migration and proliferation, significantly contributing to tumor development. We aim to investigate the role of THBS1 in TSCC. Differentially expressed genes (DEGs) were screened by sequencing using macrophages obtained from TSCC patients. Hub genes were identified from protein-protein interaction (PPI) networks. Proliferation, migration, and invasion were assessed to determine the role of THBS1 in TSCC cells. Hematoxylin-eosin staining and immunohistochemistry were utilized to explore the effect of THBS1 on xenograft models. Western blot was used to determine protein expression related to M2 macrophages, angiogenesis, epithelial-mesenchymal transition (EMT), and key pathways. MMP2, THBS1, EDN1, and PERP were hub genes of TSCC, which were upregulated in M2 macrophages. Silencing THBS1 suppressed the polarization of M2 macrophages, proliferation, migration, and invasion of TSCC cells. THBS1 silencing in M2 macrophages suppressed tumor growth in mice. THBS1 silencing in M2 macrophages inhibited angiogenesis and EMT in TSCC. TGF-β pathway was a potential downstream pathway by comprehensive bioinformatics analysis. Silencing THBS1 decreased the expression of TGF-β pathway proteins in TSCC. The activation of the TGF-β pathway induced by SRI-011381 counteracted the inhibitory impacts of THBS1 silencing on M2 macrophage polarization, proliferation, migration, and invasion of TSCC cells. THBS1 silencing inhibits the polarization of M2 macrophages to hinder TSCC progression via suppressing the TGF-β pathway.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537659","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":"Mitochondrial Genome and Phylogenetic Analysis of Rhinogobius virgigena.","authors":"Yi-Jing Zhan, Wei Hu, Kai-Rui Zhang, Cheng-He Sun","doi":"10.1007/s10528-025-11171-7","DOIUrl":"https://doi.org/10.1007/s10528-025-11171-7","url":null,"abstract":"<p><p>Rhinogobius virgigena is a fish species of the family Gobiidae, order Perciformes. This study aims to better understand the phylogenetic status of R. virgigena within Gobiidae and the phylogenetic relations in this family. Mitochondrial DNA is maternally inherited and does not recombine; therefore, mitochondrial genomes simplify genealogical tracing and reveal phylogenetic relationships among species more clearly than nuclear genomes. Therefore, we used high-throughput sequencing to obtain a complete mitochondrial genome sequence of R. virgigena and conducted phylogenetic analyses. The R. virgigena mitochondrial genome is 16,491 bp long and its base composition shows AT preference. It comprises 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a D loop. Protein-coding genes account for 69.3% of the complete genome. Leucine is the most abundant amino acid, whereas cysteine is the least abundant. tRNA genes account for 9.4% of the genome. Twenty-one tRNAs have a typical cloverleaf secondary structure, whereas tRNA-Ser1 lacks the dihydrouracil arm. The two rRNA genes are separated by tRNA-Val. A mitochondrial genome contains seven overlaps and 11 gaps, indicating a tight arrangement. Two phylogenetic trees constructed based on the nucleotide sequences of 13 protein-coding genes from 54 Gobiidae species using the maximum likelihood method and Bayesian inference revealed that R. virgigena is the most closely related to Rhinogobius duospilus.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537658","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":"Expression of PSTPIP1 in Renal Cell Carcinoma and Its Prognostic Value.","authors":"Yiyang Chen, Xiaowen Qin, Li Sun, Pu Zhang, Zhenghong Liu, Bin Zheng, Yixuan Mou, Haichang Li, Heng Wang, Dahong Zhang","doi":"10.1007/s10528-025-11163-7","DOIUrl":"https://doi.org/10.1007/s10528-025-11163-7","url":null,"abstract":"<p><p>Renal clear cell carcinoma is the most common histological form of renal cancer, but targeted therapy is still lacking. PSTPIP1 is associated with multiple immune-related pathways and is higher expressed in tumors. Thus, the correlation of PSTPIP1 and ccRCC (clear cell renal cell carcinoma) was studied to evaluate the therapeutic potential of PSTPIP1 as a target for tackling ccRCC. The expression of PSTPIP1 mRNA in clear cell renal cell carcinoma (ccRCC) was analyzed using the Oncomine, TCGA, UALCAN, GSCA, and GEPIA databases and analysis tools. Immunohistochemistry (IHC) was utilized to detect PSTPIP1 protein in clinical samples, and the chi-square test, univariate analysis and multivariate analysis were utilized to verify the relationship between PSTPIP1 and ccRCC. Co-expressed genes and enriched pathways were obtained from the TCGA and GSEA (Gene Set Enrichment Analysis) database and analysis tool. A protein-protein interaction network was constructed to support mechanism analysis. PSTPIP1 expression was significantly elevated in ccRCC tissues compared with normal renal tissues. PSTPIP1 expression levels showed significant correlations with tumor size, TNM stage, and PD-L1 status. Overexpression of PSTPIP1 was closely associated with patient survival, with high PSTPIP1 expression serving as a prognostic factor for reduced overall survival in ccRCC patients. Our findings indicate that high expression of PSTPIP1 is a predictor of poor prognosis in ccRCC patients, suggesting this protein may represent a potential therapeutic target for ccRCC treatment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537655","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 Seven Selected Genetic Polymorphisms in DNA Repair-Related Genes and Breast Cancer Risk: Evidence from a Comprehensive Meta-analysis Including 96 Studies.","authors":"Jiangyi Ruan, Hang Zhou, Zhengyu E, Yuping Chu, Shujing Zhang, Jiaxi Liao, Weiguang Zhou, Bifeng Chen","doi":"10.1007/s10528-025-11181-5","DOIUrl":"https://doi.org/10.1007/s10528-025-11181-5","url":null,"abstract":"<p><p>Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Until now, multiple genetic polymorphisms in DNA repair-related genes have been extensively examined for their contribution to breast cancer (BC) risk, including BRCA1 gene rs799917, RAD51 gene rs1801321 and rs1801320, XRCC3 gene rs861539, XPC gene rs2228001, ERCC1 gene rs3212986, and XRCC1 gene rs25487. However, these studies have yielded conflicting results. To resolve the discrepancies and provide a more precise estimation of the association between these genetic polymorphisms and BC risk, a comprehensive meta-analysis including 96 studies was carried out. The statistical results indicated that rs1801320 in the Caucasian population, rs3212986 in the total population, and rs25487 in the Asian population were significantly associated with BC risk after Bonferroni correction. Collectively, our findings suggested that RAD51 gene rs1801320, ERCC1 gene rs3212986, and XRCC1 gene rs25487 may serve as the susceptible loci in BC pathogenesis, which are warranted to be confirmed and reinforced in future studies.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525864","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":"Neuroprotective Role of THBS2 in Experimental Spinal Cord Injury Via its Anti-neuroinflammatory and Anti-apoptotic Properties.","authors":"Zheng Xu, Lixun Yang, Jianwei Du, Xiancheng Dai, Rao Xu, Jingcheng Wang","doi":"10.1007/s10528-025-11160-w","DOIUrl":"https://doi.org/10.1007/s10528-025-11160-w","url":null,"abstract":"<p><p>Thrombospondin 2 (THBS2), belongs to the platelet reactive protein family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-cell and cell-matrix interactions. Recently, a sequencing study suggested that THBS2 may be involved in the progression of spinal cord injury (SCI). This study aims to explore the expression pattern and the possible role of THBS2 in SCI, and the signaling pathway that THBS2 mainly relies on for its function. In the present study, we collected clinical samples and established both a rat model and a cell model of SCI. The expression of THBS2 in the model and clinical samples was detected by western blot assay/immunofluorescence and RT-qPCR. After establishing the rat SCI model, Basso-Beattie-Bresnahan (BBB) behavioral scores were used to detect changes in motor function. Spinal cord water content measurement was used to assess spinal cord edema in rats. To investigate the effect of THBS2 on SCI models, THBS2- expressing plasmid/THBS2-siRNA/SB 202190 (p38MAPK pathway inhibitor)/p38 agonist was applied to the rat SCI models and PC12 cell SCI model. Hematoxylin-eosin (H&E) staining was used to detect spinal cord lesions in rats. TUNEL and flow cytometry (FCM) assays were conducted to determine the apoptosis level, both in vivo and in vitro. Cell viability was determined by CCK-8 assay. Changes in inflammatory factor (TNF-α, IL-1β and IL-6) levels in models were quantified by enzyme linked immunosorbent assay (ELISA). Finally, p38MAPK signaling pathway-related proteins and apoptosis-related proteins were detected by western blot assay. The expression of THBS2 showed a gradual increase and decrease process after SCI, with the most significant increase observed in the mid-phase of SCI. THBS2-expressing plasmid and SB 202190 significantly increased BBB score scores, while decreased spinal cord water content. Also, the H&E staining results suggested that overexpression of THBS2-plasmid and SB 202190 could inhibit spinal cord lesions. THBS2 and SB 202190 treatment significantly enhanced the cell ability of LPS-induced PC12 cells. In addition, THBS2-expressing plasmid and SB 202190 inhibited the level of apoptosis and suppressed the secretion of inflammatory factors in both in vivo and in vitro models. Moreover, overexpression of THBS2 inhibited the activation of the p38MAPK signaling pathway in SCI models, and p38 agonist reversed the protective effects of THBS2-plasmid on SCI rats and LPS-induced PC12 cells. In addition, THBS2 down-regulation further promote LPS-induced apoptosis and inflammatory response in PC12 cells. THBS2 was highly expressed in SCI, and overexpression of THBS inhibited the activation of the MAPK signaling pathway and thus protects against SCI.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504407","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":"Circ_0001461 Regulates Colorectal Cancer Growth, Movement and Immune Escape Through miR-532-3p/AMOTL2.","authors":"Wei Zheng, Hong Liang, Chao Zhang","doi":"10.1007/s10528-025-11162-8","DOIUrl":"https://doi.org/10.1007/s10528-025-11162-8","url":null,"abstract":"<p><p>Colorectal cancer (CRC), as a common malignant tumor of gastrointestinal tract, has become one of the important diseases threatening human health. Circ_0001461 has been proven to be closely associated with the occurrence and development of various cancers. This study explored the function and possible mechanism of circ_0001461 in CRC. The RNA expression level was detected using qRT-PCR. The viability, apoptosis or invasion ability of CRC cells were explored by CCK-8, flow cytometry or Transwell experiment, respectively. The protein expression level in cells was analyzed by Western blot (WB). IFN-γ, IL-2 or TNF-α levels were investigated via ELISA experiment. The targeting relationship between circ_0001461, miR-532-3p and AMOTL2 was confirmed via dual-luciferase reporter experiment, RNA pull-down experiment and RIP assay. The protein expression in tissues was explored by IHC staining. Tumor volumes, body weights, tumor weights and apoptosis levels were detected in xenograft mouse model. Circ_0001461 was greatly expressed in CRC samples and was associated with poor prognosis. Silencing circ_0001461 reduced cell proliferation, increased cell apoptosis rate, decreased invasion ability and inhibited immune escape in vitro. Additionally, silencing circ_0001461 prominently shortened the tumor volume and tumor weight in vivo. Circ_0001461 targeted miR-532-3p to regulate AMOTL2 expression. AMOTL2 was the downstream targets of miR-532-3p. Downregulation of miR-532-3p or overexpression of AMOTL2 abolished the effect of silencing circ_0001461. Collectively, our research demonstrated that the circ_0001461 played a certain regulatory role in growth, movement and immune escape of colon cancer via miR-532-3p/AMOTL2 axis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493323","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":"NSUN3-Mediated ROS Accumulation Promotes Hepatocellular Carcinoma Proliferation and Activates PI3K/AKT Pathway.","authors":"Haodong Liu, Shijie Liang, Chunting Peng, Jiawei Yang, Zheng Yang, Wuning Mo","doi":"10.1007/s10528-025-11158-4","DOIUrl":"https://doi.org/10.1007/s10528-025-11158-4","url":null,"abstract":"<p><p>NSUN3 (NOP2/Sun RNA methyltransferase family member 3) is a gene encoding an RNA methyltransferase primarily responsible for specific methylation modifications on mitochondrial tRNA. Recent studies have indicated that aberrant expression of NSUN3 may be associated with the development of a range of tumors. UALCAN and GEPIA2 were utilized for bioinformatics analyses, while lentiviral vectors and small interfering RNA techniques were employed to create cell lines with either overexpression or silencing of NSUN3. To assess the impact of NSUN3 on hepatocellular carcinoma cells in vitro, CCK-8 assays, apoptosis assays, and cell cycle analyses were conducted. The accumulation of ROS mediated by NSUN3 was evaluated using fluorescent probes specific for ROS. Additionally, Western blotting was performed to verify transfection efficiency and to analyze the expression levels of the PI3K/AKT signaling pathway and BCL-2 protein. The findings of the current investigation indicate that NSUN3 is markedly overexpressed in HCC and is associated with a negative prognosis. The role of NSUN3 in modulating mitochondrial energy metabolism implies that its overexpression may facilitate the proliferation of HCC cells through the promotion of ROS accumulation. In contrast, the silencing of NSUN3 has been demonstrated to hinder the proliferation of HCC cells. Furthermore, the results also indicate that NSUN3 has the capacity to activate the PI3K/AKT signaling pathway, this resulted in the preliminary clarification of the molecular mechanisms at play. In summary, our research addresses the functional role of NSUN3 in HCC. The initial identification of NSUN3 suggests that it may serve as a promising target for the development of novel therapeutic strategies in the treatment of HCC.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473643","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}