Functional & Integrative Genomics最新文献

Verticillium dahliae, a soil-borne pathogen, poses a threat to cotton production, causing wilting and quality issues. While progress has been made in understanding the interaction between cotton and V. dahliae, many molecular aspects of the defense mechanisms of cotton remain unclear. Cotton primarily relies on preformed defense structures, including cuticle synthesis and phenolic compound production, along with physiological and biochemical reactions. Current defense strategies involve preventing reactive oxygen species accumulation and inducing systemic acquired resistance. This study underscores the importance of these mechanisms and highlights the potential for genetic and molecular engineering to enhance resistance of cotton against Verticillium wilt, offering insights for future breeding of resilient cotton varieties.

Intervertebral disc degeneration (IDD) is a prevalent and multifactorial musculoskeletal disorder driven by complex genetic predispositions and dysregulated molecular pathways. While genetic contributions to IDD are widely recognized, the functional roles and therapeutic potential of specific causal genes remain incompletely characterized. To systematically identify novel and robust therapeutic targets, we performed an integrated multi-omics analysis. This approach integrated Mendelian randomization (MR) using large-scale GWAS summary statistics with QTL data, scRNA-seq, and bulk RNA-seq to prioritize candidate genes. Our analysis identified AKR1C1 as a candidate gene with a causal role in IDD pathogenesis. Subsequent in vitro functional studies demonstrated that elevated AKR1C1 expression activates the PI3K/AKT pathway, thereby reducing ROS accumulation and lipid peroxidation and ultimately inhibiting ferroptosis in nucleus pulposus (NP) cells. These findings indicated that AKR1C1 may be a promising therapeutic target for mitigating IDD.

Polyamines are small, aliphatic, nitrogenous bases that play vital roles in the growth and development of organisms. In certain cereal crops, polyamines regulate grain growth and development, and exogenous application can considerably enhance grain-filling efficiency and grain quality. However, the functions of genes associated with polyamine metabolism in foxtail millet (Setaria italica L.) remain poorly characterized. In this investigation, nine genes related to polyamine metabolism, belonging to five gene families, were identified in foxtail millet. These nine genes are distributed across three of the nine chromosomes. The cis-acting elements in these gene promoters are primarily related to plant growth and development, environmental stress, and hormone response. Transient expression experiments revealed that SiSPDS2 is located in the cytoplasm and nucleus. In Arabidopsis, SiSPDS2 overexpression increased seed spermidine content and significantly enhanced plant height, silique length, seed size, and 1000-seed weight, suggesting that SiSPDS2 can positively regulate seed growth and development. This study provides a theoretical basis for further research into the role of polyamines in the growth and development of foxtail millet.

Background Emerging evidence indicates that C6ORF120 is highly expressed in the liver and may modulate immune responses in various hepatic disorders. However, its role in hepatic lipid metabolism and metabolic dysfunction-associated steatotic liver disease (MASLD) is unexplored. This study aimed to elucidate the effects and potential mechanisms of C6ORF120 on hepatic lipogenesis. Methods C6ORF120 expression in MASLD was assessed using patient serum and the Gene Expression Omnibus (GEO) database. A high-fat diet-induced MASLD model was established in C6orf120-KO rats. Fatty acid-induced lipid accumulation models were generated in primary hepatocytes, HepG2 and Huh7 cells. These models were employed to investigate the effects of C6ORF120 on hepatic lipogenesis and MASLD progression. Results C6ORF120 expression was significantly upregulated in MASLD patients and obese rat models. Genetic deletion of C6ORF120 markedly alleviated high-fat diet-induced steatosis in the liver of rats. In vitro, C6orf120 gene deficiency attenuated lipid accumulation and suppressed key lipogenic genes (such as fatty acid synthase (Fasn), phospho-acetyl coenzyme carboxylase (p-ACC), sterol regulatory element binding protein-1c (Srebp1c)) in primary hepatocytes and HepG2 cells. Conversely, C6ORF120 overexpression increased lipid accumulation in HepG2 cells. RNA sequencing analysis showed that lipid metabolism pathway and peroxisome proliferators activated receptor (PPAR) signaling pathway were significantly altered in the liver of C6orf120-KO rats. We demonstrated that C6ORF120 may regulate lipid metabolism through the hepatic PPARα, which is involved in fatty acid production and lipid oxidation. Further, we found that serum C6ORF120 expression was correlated with clinical indicators in patients with MASLD. Conclusion This study preliminarily revealed a novel function for C6ORF120 in hepatic lipid metabolism via affecting the PPAR pathway. The result identifies C6ORF120 as a novel regulator of hepatic lipid metabolism through PPARα-dependent mechanisms, offering potential therapeutic targets for MASLD.

The escalating concerns of environmental protection and global food security are exacerbated by biotic and abiotic stresses, including drought, heat waves, cold shocks, and flooding, all of these significantly reduce crop yields and threaten food supply. Climate change amplifies these challenges, imposing a severe impact on agricultural productivity and food security globally. To address these challenges, it is crucial to enhance food production through the development of climate resilient crops, with a focus on crops that are resistant to both abiotic and biotic stresses. This can be achieved through conventional breeding, biotechnology, and advanced omics techniques such as transcriptomics, proteomics, and metabolomics. These approaches have illuminated key genes, proteins, and metabolic pathways that are critical for improving crop resilience. Sustainable farming practices, including intercropping, agroforestry, and the use of biofertilizers and biochar, are also key strategies for improving soil structure and water retention. Furthermore, supportive policies such as agricultural extension services, collaboration between public and private sectors, and farmer education on climate resilient crops are essential for fostering climate resilience in agriculture. This review consolidates current knowledge and highlights the role of these strategies in tackling food insecurity, with a focus on the genomic innovations that underpin climate resilience in plants.

Bergenia ciliata is a priority medicinal plant, renowned for its antiviral, antibacterial, anticancer, and anti-inflammatory properties. Despite its extensive use, the underlying molecular mechanisms of specialized bioactive metabolites biosynthesis remain largely unexplored. Next-generation sequencing-assisted organ-specific in-depth transcriptional analysis of leaf, stem, and root rhizome yielded 259 million high-quality paired-end reads, which were de novo assembled into 73,039 unigenes and 28,599 isoforms. Functional annotation revealed extensive gene functions significantly enriched in KEGG pathways related to secondary metabolism, including flavonoid, terpenoid, and phenylpropanoid biosynthesis. Moreover, differential expression analysis identified 15,395 transcripts, including key gene families such as TFs (bHLH, NAC, and MYB-related), CYPs, and UGTs that exhibited notable tissue-specific dynamic expression driving the secondary metabolite biosynthesis. Further, pathway enrichment of candidate DEGs highlighted organ-specific unique gene expression patterns that substantially contributed toward the biosynthesis of gallic acid, bergenin, phenylpropanoid, and flavonoids. Untargeted metabolomic profiling further revealed DAMs that strongly correlated with transcriptome profiles, confirming the tissue-specific regulation of these metabolites. Integration of transcriptomic and metabolomic data unraveled distinct molecular signatures and regulatory hubs involved in specialized metabolite pathways. Additionally, the GRN predicted significant interactions between TFs (bHLH, C2H2, bZIP, ERF, and B3) and key biosynthetic genes. Further, qRT-PCR validation reinforces the transcriptomic data and emphasizes the importance of this study. Overall, this study provides the first comprehensive genomic resource for B. ciliata, revealing key genes, pathways, and regulators involved in gallic acid and flavonoid biosynthesis. These findings lay a robust foundation for metabolic engineering, conservation strategies, and industrial-scale exploitation of bioactive compounds.

Long noncoding RNAs (lncRNAs) are noncoding transcripts longer than 200 nucleotides that play crucial roles in regulating gene expression and various physiological processes. In cattle, a species of major agricultural importance, lncRNAs hold significant potential for improving key economic traits such as meat and milk production. Unlike previous reviews that often focus on a single trait or species, this article provides a systematic comparison of lncRNA applications in two distinct production systems: meat traits in beef cattle and milk production traits in dairy cattle. By synthesizing recent advances, we aim to maximize the understanding of lncRNAs' roles in cattle breeding, and to establish a foundational theoretical framework that can guide future research and practical breeding efforts.

Colon cancer is one of the leading causes of cancer-related mortality, with liver metastasis commonly complicating its progression and significantly worsening patient prognosis. This study aims to explore the relationship between liver metastasis in colon cancer and various clinicopathological factors, as well as to investigate the underlying molecular mechanisms. The clinical data and weighted gene co-expression network analysis (WGCNA) were used to identify key genes associated with liver metastasis. The results revealed significant alterations in lipid metabolism associated with colon cancer progression. Notably, WGCNA and machine learning algorithms identified cardiolipin synthase 1 (CRLS1) as a hub gene robustly associated with liver metastasis in colon cancer. The expression of CRLS1 was assessed via scRNA-seq and the collection of clinical samples from colon cancer patients. CRLS1 knockdown significantly inhibited the proliferation and migration of colon cancer cells and suppressed lipid metabolism. Finally, several candidate drugs have been identified that may effectively target CRLS1. Moreover, it has been confirmed that the mTOR signaling pathway regulates CRLS1 expression, offering a promising avenue for future therapeutic strategies. In conclusion, this study highlights the pivotal role of CRLS1 in colon cancer and its potential as a biomarker and therapeutic target through lipid metabolism in managing this aggressive disease.

Cervical cancer (CC) is a major malignancy and a serious threat to women’s health worldwide. The role of FAM72A in CC remains poorly defined. This study aimed to investigate its function in CC progression and its impact on the PI3K/AKT/mTOR pathway. FAM72A expression in CC was examined using TCGA-CESC and GEO (GSE63514) datasets, and then validated in CC tissues and cell lines. Functional assays assessed cell proliferation (CCK-8, EdU), invasion (Transwell), apoptosis (flow cytometry), and epithelial–mesenchymal transition (EMT; Western blot for E-cadherin/N-cadherin). The role of FAM72A in the PI3K/AKT/mTOR pathway was further evaluated by Western blot and pharmacological modulation with the activator 740 Y-P and the inhibitor LY294002. In vivo, a xenograft model with BALB/c nude mice was used to assess tumor growth, apoptosis (TUNEL staining), proliferation (Ki-67 IHC), and pathway activation (p-PI3K, p-AKT, and p-mTOR). FAM72A expression was upregulated in CC tissues and correlated with poor survival. Subgroup analysis showed that high FAM72A expression was associated with advanced FIGO stage, lymph node metastasis, and deep stromal invasion, indicating a link with aggressive clinical features. FAM72A silencing suppressed proliferation and invasion but promoted apoptosis, mainly through inhibition of the PI3K/AKT/mTOR pathway. Conversely, FAM72A overexpression enhanced these malignant traits. In vivo, FAM72A knockdown reduced tumor burden and altered EMT markers and PI3K/AKT/mTOR pathway activity. FAM72A promotes CC progression, at least in part, through activation of the PI3K/AKT/mTOR pathway, supporting its value as a potential therapeutic target.