Genes & genomics最新文献

{"title":"Transcriptome analysis of the effect of HERV-K env gene knockout in ovarian cancer cell lines","authors":"Eun-Ji Ko, Dong Soo Suh, Hongbae Kim, Ji Young Lee, Wan Kyu Eo, Heungyeol Kim, Ki Hyung Kim, Hee-Jae Cha","doi":"10.1007/s13258-024-01544-4","DOIUrl":"https://doi.org/10.1007/s13258-024-01544-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of various diseases, particularly cancers. Previous investigations from our group demonstrated that targeted knockout (KO) of the HERV-K <i>env</i> gene led to a significant reduction in tumorigenic attributes, including proliferation, migration, and invasion of ovarian cancer cells.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>In this study, we aimed to elucidate the impact of HERV-K <i>env</i> KO on gene expression in ovarian cancer cell lines through comparative RNA sequencing (RNA-Seq) analysis with two distinct HERV-K <i>env</i> KO ovarian cancer cell lines, SKOV3 and OVCAR3.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>HERV-K <i>env</i> gene KO was achieved in SKOV3 and OVCAR3 ovarian cancer cell lines using the CRISPR-Cas9 system. Next-generation mRNA sequencing was employed to assess the gene expression profiles of both mock and HERV-K <i>env</i> KO ovarian cancer cells. Furthermore, comprehensive analyses involving gene ontology and pathway assessments were conducted.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Transcriptome analysis revealed that 23 differentially expressed genes (DEGs) were upregulated and 17 DEGs were downregulated in SKOV3 cells. In OVCAR3 cells, 198 DEGs were upregulated, and 17 DEGs were downregulated. Notably, 53 DEGs exhibited statistically significant differences among the 1,612 DEGs identified. Our findings indicate that HERV-K <i>env</i> gene KO exerts a profound influence on gene expression patterns in OVCAR3 cells, while genetic alterations in expression were relatively modest in SKOV3 cells. Nevertheless, genes <i>ND1</i>, <i>ND2</i>, and <i>CYTB</i> displayed a common increase in expression, while <i>ERRFI1</i> and <i>NDRG1</i> exhibited a decrease in expression in both cell lines.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our study demonstrates that KO of the HERV-K <i>env</i> gene in ovarian cancer cell lines has a substantial impact on gene expression patterns and can be used to identify potential therapeutic targets for ovarian cancer and related diseases.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261706","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 TGF-β/BMP signaling pathway polymorphisms and the risk of primary ovarian insufficiency in Korean women","authors":"Yong Hyun Ha, Ji Hyang Kim, Chang Soo Ryu, Ji Won Kim, Eun Ju Ko, Jeong Yong Lee, Ji Eun Shin, Young Ran Kim, Eun Hee Ahn, Nam Keun Kim","doi":"10.1007/s13258-024-01564-0","DOIUrl":"https://doi.org/10.1007/s13258-024-01564-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Primary ovarian insufficiency (POI) is one of the leading female infertility diseases in which ovarian function stops before the age of 40. Reports that POI is associated with transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) signaling pathway–associated genes (e.g., TGF-β, and BMP15) have been continuous since publication that the TGF-β superfamily acts as important regulators for ovary and placenta function in humans. Mechanistically, the secretion of follicle-stimulating hormone, progesterone, and estrogen is affected by the TGF-β superfamily in granulosa cells, which are involved in the development of theca cells, oocytes, and granulosa cells.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study aimed to identify the association between genes related to the TGF-β/BMP signaling pathway and the risk of POI pathogenesis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Possible associations between six gene polymorphisms and POI susceptibility were examined in 139 patients with POI and 345 control subjects.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Allele combination of <i>TGFBR</i>1 rs334348 G &gt; A and <i>TGFBR3</i> rs1805110G &gt; A exhibited association with decreased POI risk (adjusted odds ratio [AOR] = 0.165; 95% confidence interval [CI] 0.032–0.847; <i>P</i> = 0.031). Also, <i>TGFBR1</i> rs1590 G &gt; T and rs334348 G &gt; A and <i>TGFBR3</i> rs1805110 G &gt; A allele combination exhibited association with decreased POI risk (OR = 0.553; 95% CI 0.374–0.816; <i>P</i> = 0.003).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study suggests that polymorphisms in the TGF-β signaling pathway genes can be useful biomarkers for POI diagnosis and treatment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194604","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":"Transcriptome-based screening and validation of key genes for wool color in cashmere goats","authors":"Remila Apar, Xiaofang Ye, Xuefeng Lv","doi":"10.1007/s13258-024-01562-2","DOIUrl":"https://doi.org/10.1007/s13258-024-01562-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Colored wool from cashmere goats is increasingly popular among consumers, but the transcriptomic differences between coat colors are poorly understood.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This study aimed to screen for coat color regulation-associated genes in cashmere goats to ascertain their underlying molecular mechanisms.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Transcriptomic sequencing of skin tissues from black (BC), brown (YC), and white cashmere (WC) goats was performed. Immunohistochemistry and western blotting were used to validate SLC24A4 and DCT expression, two essential genes identified for coat color determination.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We identified 6,518 differentially expressed genes (DEGs) in the BC vs. WC group (3,919 upregulated, 2,599 downregulated). Next, 5,593 DEGs were identified in the YC vs. WC group (3,629 upregulated, 1,964 downregulated). Finally, 4,538 DEGs were expressed in both groups, with 1,980 and 1,055 DEGs exclusively expressed in either group. Functions and pathways associated with hair color were enriched, including melanosomes, melanocyte migration, melanin biosynthesis processes and functions, and melanogenesis pathways. <i>TYRP1</i>, <i>SLC24A4</i>, <i>PMEL</i>, <i>OCA2</i>, and <i>DCT</i> were significantly upregulated in BC goat skin, while <i>ASIP</i> was significantly upregulated in YC skin. Additionally, <i>KIT</i>, <i>POMC</i>, <i>SLC24A5</i>, <i>Wnt3a</i>, and <i>EDN3</i> were DEGs for different coat colors. Immunohistochemistry revealed SLC24A4 and DCT expression in dermal papillae, inner and outer root sheaths, and the hair follicle matrix. Western blotting showed that SLC24A4 protein levels were highest in BC goat skin. DCT protein levels were also highest in BC goat skin, albeit not significantly.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These results further our understanding of coat color regulation in cashmere goats, establishing a foundation for their molecular breeding.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194606","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":"Cytogenetic analysis and visualization of genetic relationships in wild lilies","authors":"Ji-Yun Kang, Ki-Byung Lim, Yun-Jae Ahn","doi":"10.1007/s13258-024-01568-w","DOIUrl":"https://doi.org/10.1007/s13258-024-01568-w","url":null,"abstract":"<p>Lilies are highly regarded for their ornamental appeal and striking flowers, which are of significant importance in horticulture. Understanding the genetic makeup of these plants is crucial for breeding and developing new cultivars. This study presents a comprehensive cytogenetic analysis of 45 S and 5 S rDNA loci in 34 wild <i>Lilium</i> species. To reveal the genetic relationships within the genus, advanced visualization methods, such as heatmaps and 3D network plots, were utilized. The results of this study identified both conserved and divergent genetic features, which offer insights into the evolutionary history and potential genetic compatibility of these species. Notably, the clustering of species based on rDNA locus patterns highlights the need for potential taxonomic re-evaluation and reveals candidates for cross-breeding. This integrated approach emphasizes the importance of combining cytogenetic data with traditional morphological classifications to refine our understanding of the <i>Lilium</i> species. Future research should expand the range of analyzed species, incorporate additional molecular markers to further elucidate genetic relationships, and support the development of resilient and diverse ornamental crops. The findings of this study provide a novel framework for genetic analysis of <i>Lilium</i>, offering valuable insights for both scientific understanding and practical breeding programs.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194605","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":"Contents of paeoniflorin and albiflorin in two Korean landraces of Paeonia lactiflora and characterization of paeoniflorin biosynthesis genes in peony.","authors":"Seungki Lee, Nam-Il Park, Yeri Park, Kweon Heo, Yongsoo Kwon, Eun Sil Kim, Youn Kyoung Son, Kyung Jin Lee, Seung Young Choi, Beom-Soon Choi, Nam-Soo Kim, Ik-Young Choi","doi":"10.1007/s13258-024-01553-3","DOIUrl":"10.1007/s13258-024-01553-3","url":null,"abstract":"<p><strong>Background and research purpose: </strong>Paeoniflorin and albiflorin are monoterpene glycosides that exhibit various medicinal properties in Paeonia species. This study explored the terpene biosynthesis pathway and analyzed the distribution of these compounds in different tissues of two Korean landraces of Paeonia lactiflora to gain insights into the biosynthesis of monoterpene glycosides in P. lactiflora and their potential applications.</p><p><strong>Materials and methods: </strong>Two Korean landraces, Hongcheon var. and Hwacheon var, of P. lactiflora were used for the analyses. Contents of the paeoniflorin and albiflorin were analyzed using HPLC. RNA was extracted, sequenced, and subjected to transcriptome analysis. Differential gene expression, KEGG, and GO analyses were performed. Paeoniflorin biosynthesis genes were isolated from the transcriptomes using the genes in Euphorbia maculata with the NBLAST program. Phylogenetic analysis of of 1-Deoxy-D-xylulose 5-phosphate synthase (DOXPS), geranyl pyrophosphate synthase (GPPS), and pinene synthase (PS) was carried out with ClustalW and MEGA v5.0.</p><p><strong>Results and discussion: </strong>Analysis of paeoniflorin and albiflorin content in different tissues of the two P. lactiflora landraces revealed significant variation. Transcriptome analysis yielded 36,602 unigenes, most of which were involved in metabolic processes. The DEG analysis revealed tissue-specific expression patterns with correlations between landraces. The isolation of biosynthetic genes identified 173 candidates. Phylogenetic analysis of the key enzymes in these pathways provides insights into their evolutionary relationships. The sequencing and analysis of DOXPS, GPPS, PS revealed distinct clades and subclades, highlighting their evolutionary divergence and functional conservation. Our findings highlight the roots as the primary sites of paeoniflorin and albiflorin accumulation in P. lactiflora, underscoring the importance of tissue-specific gene expression in their biosynthesis.</p><p><strong>Conclusion: </strong>this study advances our understanding of monoterpene glycoside production and distribution in Paeonia, thereby guiding further plant biochemistry investigations.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912385","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":"Characterization of the complete mitochondrial genome of a newly discovered torrent catfish, Liobagrus geumgangensis, and their phylogenetic relationships.","authors":"Seung-Woon Yun, Jong-Young Park","doi":"10.1007/s13258-024-01552-4","DOIUrl":"10.1007/s13258-024-01552-4","url":null,"abstract":"<p><strong>Background: </strong>A new Liobagrus fish was reported from the Korean Peninsula, but research on this taxon is lacking. Moreover, existing research on the mitogenome of the genus Liobagrus in Korea is very limited, and no studies have been conducted on structural characteristics of transfer RNA (tRNA) or gene order comparisons between taxa; instead, research has been restricted to basic phylogeny.</p><p><strong>Objective: </strong>The complete mitochondrial genome of Liobagrus geumgangensis was analyzed for the first time. We then aimed to reconstruct the phylogenetic relationships of the genus Liobagrus and estimate the divergence time of speciation events.</p><p><strong>Methods: </strong>We used a dissected fin clip from an adult of Liobagrus geumgangensis. Genomic DNA was extracted and analyzed with whole genome sequencing (WGS) and assembled by the NOVOPlasty method. The mitogenome sequence was annotated, and a genome map, tRNA structure, and phylogenetic tree were constructed using maximum likelihood analysis. In addition, divergence time was estimated.</p><p><strong>Results: </strong>The mitochondrial genome was 16,522 bp in length and comprised 37 genes. The overall base composition was 30.5% A, 25.5% T, 28.4% C, and 15.7% G. Most tRNAs exhibited the typical clover leaf shape, except trnS1. Phylogenetic analysis revealed that Liobagrus geumgangensis clustered within a clade with four other Liobagrus species exclusive to the southern region of the Korean Peninsula. Its divergence was estimated to have occurred during the late Miocene.</p><p><strong>Conclusion: </strong>Characteristics of Liobagrus geumgangensis mitogenome were consistent with those of other torrent catfish species. Time scale estimation revealed distinct groupings, with some distributed across mainland Asia and others in the southern region of the Korean Peninsula. Notably, the Korean Peninsula group was identified as its own lineage, comprising entirely endemic species.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912384","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":"Gut Microbiome and colorectal cancer: discovery of bacterial changes with metagenomics application in Turkısh population.","authors":"Yakup Ulger, Anıl Delik, Hikmet Akkız","doi":"10.1007/s13258-024-01538-2","DOIUrl":"10.1007/s13258-024-01538-2","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the 3rd most common cancer in the world and colonic carcinogenesis is a multifactorial disease that involves environmental and genetic factors. Gut microbiota plays a critical role in the regulation of intestinal homeostasis. Increasing evidence shows that the gut microbiome plays a role in CRC development and may be a biomarker for early diagnosis.</p><p><strong>Objective: </strong>This study aimed to determine the clinical prognostic significance of gut microbiota in CRC patients in the Turkish population by metagenomic analysis and to determine the microbial composition in tumor tissue biopsy samples.</p><p><strong>Methods: </strong>Tissue biopsies were taken from the participants with sterile forceps during colonoscopy and stored at -80 °C. Then, DNA isolation was performed from the tissue samples and the V3-V4 region of the 16 S rRNA gene was sequenced on the Illumina MiSeq platform. Quality control of the obtained sequence data was performed. Operational taxonomic units (OTUs) were classified according to the Greengenes database. Alpha diversity (Shannon index) and beta diversity (Bray-Curtis distance) analyses were performed. The most common bacterial species in CRC patients and healthy controls were determined and whether there were statistically significant differences between the groups was tested.</p><p><strong>Results: </strong>A total of 40 individuals, 13 CRC patients and 20 healthy control individuals were included in our metagenomic study. The mean age of the patients was 64.83 and BMI was 25.85. In CRC patients, the level of Bacteroidetes at the phylum taxonomy was significantly increased (p = 0.04), the level of Clostridia at the class taxonomy was increased (p = 0.23), and the level of Enterococcus at the genus taxonomy was significantly increased (p = 0.01). When CRC patients were compared with the control group, significant increases were detected in the species of Gemmiger formicilis (p = 0.15), Prevotella copri (p = 0.02) and Ruminococcus bromii (p = 0.001) at the species taxonomy.</p><p><strong>Conclusions: </strong>Metagenomic analysis of intestinal microbiota composition in CRC patients provides important data for determining the treatment options for these patients. The results of this study suggest that it may be beneficial in terms of early diagnosis, poor prognosis and survival rates in CRC patients. In addition, this metagenomic study is the first study on the colon microbiome associated with CRC mucosa in the Turkish population.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579456","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":"A novel compound heterozygous mutation of UFC1 in a patient with neurodevelopmental disorder.","authors":"Ye Han, Yangyang Ge, Haoran Liu, Liying Liu, Lina Xie, Xiaoli Chen, Qian Chen","doi":"10.1007/s13258-024-01543-5","DOIUrl":"10.1007/s13258-024-01543-5","url":null,"abstract":"<p><strong>Background: </strong>Neurodevelopmental disorders (NDDs) encompass a diverse group of disorders characterized by impaired cognition, behavior, and motor skills. Genetic factor is the leading cause in about 35% of NDDs patients. Mutations of UFC1, an E2 enzyme participating in the post-translational modification of proteins through attachment of ubiquitin-like proteins, were recently reported to be associated with NDDs. However, the UFC1 associated NDDs are rare and the data are scarce, thus making it difficult to identify this disease.</p><p><strong>Objective: </strong>This study reported a novel compound heterozygous mutation of UFC1 in a Chinese patient with NDD.</p><p><strong>Methods: </strong>Detailed clinical data were recorded. Whole exome sequencing (WES) was performed to determine the genetic cause of the patient. The candidate mutation was verified using Sanger sequencing.</p><p><strong>Results: </strong>WES analysis identified a novel compound heterozygous mutation of UFC1 (c.19 C > T, p.Arg7* and c.164G > A, p.Arg55Gln). The nonsense mutation c.19 C > T (p.Arg7*) led to a premature truncation of UFC1 and nonsense-mediated RNA decay. Arg55 is highly conserved among orthologues. Molecular modeling predicted that mutation c.164G > A (p.Arg55Gln) may influence the correct folding of UFC1. These two mutations were evaluated as likely pathogenic based on the ACMG guideline. Moreover, neurodevelopmental delay, microcephaly, and epilepsy were confirmed as major phenotypes of UFC1 mutation.</p><p><strong>Conclusion: </strong>This study expands the mutational spectrum of NDDs. We reported the nonsense mutation of UFC1 for the first time. We also confirmed the major phenotypes that may guide clinical identification of UFC1 mutation. Ubiquitination mechanism is highlighted in NDDs pathogenesis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792299","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":"Heterogeneity of hepatocellular carcinoma that responds differently to combination therapy with TACE and Sorafenib as determined by digital spatial gene expression profiling.","authors":"Chenhao Xu, Renyi Su, Zhengyang Lu, Yisu Song, Xiaobing Zhang, Wenzhi Shu, Zhe Yang, Runzhou Zhuang, Xiao Xu, Xuyong Wei","doi":"10.1007/s13258-024-01548-0","DOIUrl":"10.1007/s13258-024-01548-0","url":null,"abstract":"<p><strong>Background: </strong>The combination of Sorafenib and transcatheter arterial chemoembolization (TACE) exhibits limited efficacy in the treatment of certain advanced hepatocellular carcinomas (HCC), and the molecular mechanisms underlying resistance to this combination remain unclear.</p><p><strong>Objective: </strong>This study aims to underscore the distinctive contribution of GeoMx DSP technology in elucidating the molecular intricacies of HCC resistance to the Sorafenib and TACE combination.</p><p><strong>Methods: </strong>Patients with advanced HCC during the waiting period before liver transplantation were classified into sensitive and resistant groups based on their response to Sorafenib and TACE combination therapy. Employing GeoMx DSP technology for comprehensive gene expression profiling, we identified pivotal molecular targets linked to resistance against combination therapy.</p><p><strong>Results: </strong>The investigation scrutinized intra-tumoral and inter-individual variances, unveiling a spectrum of crucial molecular targets, such as PLG, PLVAP, immunoglobulin genes, ORM1, and NR4A1, among others. Additionally, we explored signaling pathways associated with treatment responsiveness, including the PPAR signaling pathway. Notably, we emphasized the significance of the immune microenvironment characterized by heightened SPP1 expression in HCC resistance to combination therapy. In the resistant group, SPP1⁺ tumor-associated macrophage (TAM) infiltration was notably pronounced (p = 0.037), while T-cell depletion showed a mitigated presence (p = 0.013).</p><p><strong>Conclusion: </strong>The study reveals intra- and inter-individual heterogeneity in HCC that is differentially responsive to the combination of Sorafenib and TACE, highlighting multiple key molecular targets associated with treatment resistance. The immune microenvironment is important, and in particular, SPP1⁺ TAM infiltration may play a key role. Meanwhile, the introduction of immunotherapy in patients resistant to combination therapy may lead to positive results.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792300","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":"The impact of histone lactylation on the tumor microenvironment and metabolic pathways and its potential in cancer therapy.","authors":"Juanhong Zhou, Xinyun Ma, Xiaofeng Liu, Yang Liu, Jiaojiao Fu, Yaling Qi, Huiling Liu","doi":"10.1007/s13258-024-01554-2","DOIUrl":"10.1007/s13258-024-01554-2","url":null,"abstract":"<p><strong>Background: </strong>The complexity of cancer is intricately linked to its multifaceted biological processes, including the roles of the tumor microenvironment (TME) as well as genetic and metabolic regulation. Histone lactylation has recently emerged as a novel epigenetic modification mechanism that plays a pivotal role in regulating cancer initiation, proliferation, invasion, and metastasis.</p><p><strong>Objective: </strong>This review aims to elucidate the role of histone lactylation in modulating various aspects of tumor biology, including DNA repair mechanisms, glycolytic metabolic abnormalities, functions of non-tumor cells in the TME, and the promotion of tumor inflammatory responses and immune escape. Additionally, the review explores potential therapeutic strategies targeting histone lactylation.</p><p><strong>Methods: </strong>A comprehensive literature review was performed, analyzing recent findings on histone lactylation and its impact on cancer biology. This involved a systematic examination of studies focusing on biochemical pathways, cellular interactions, and clinical implications related to histone lactylation.</p><p><strong>Results: </strong>Histone lactylation was identified as a critical regulator of tumor cell DNA repair mechanisms and glycolytic metabolic abnormalities. It also significantly influences the functions of non-tumor cells within the TME, promoting tumor inflammatory responses and immune escape. Moreover, histone lactylation acts as a multifunctional biological signaling molecule impacting immune responses within the TME. Various cell types within the TME, including T cells and macrophages, were found to regulate tumor growth and immune escape mechanisms through lactylation.</p><p><strong>Conclusion: </strong>Histone lactylation offers a novel perspective on tumor metabolism and its role in cancer development. It presents promising opportunities for the development of innovative cancer therapies. This review underscores the potential of histone lactylation as a therapeutic target, paving the way for new strategies in cancer treatment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912386","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}