Genes & genomics最新文献

Background: Dairy cattle are economically important animal resources contributing to human health and well-being by providing nutritious milk and other products. Non-coding RNAs are involved in biological processes, regulating gene expressions at the levels of messenger. However, the effects on miRNA expression and their function in dairy cattle are still unclear.

Objective: We aimed to understand better miRNA expressions associated with milk and reproduction quantitative trait loci (QTLs) and their locations in dairy cattle.

Methods: In this study, miRNA profiling was performed in blood samples collected from three non-pregnant cows using the Illumina HiSeq 2500 platform. The expression levels of miRNAs were estimated by miRDeep2 and QTLs associated with milk and reproduction were identified using cattleQTLdb. Functional enrichment analysis was performed to determine biological functions or pathways using DAVID.

Results: In total, 406 known and 562 novel expressed miRNAs were identified in three dairy cattle using miRDeep2. A total of 27,652 and 31,064 QTLs associated with milk and reproduction traits were identified by QTL mapping for known and novel miRNAs, respectively. Of these, 1835 and 1020 miRNAs were related to milk and reproduction traits, respectively.

Conclusion: Our study provides a basis for further research to understand the miRNA expressions in dairy cattle and their role in milk and reproduction traits. We suggest that miRNAs may be helpful as biomarkers for improving milk and reproduction traits in dairy cattle through genetic selection.

Background: High-grade serous ovarian cancer (HGSOC) is the most aggressive ovarian cancer subtype, characterized by high recurrence, chemoresistance, and poor prognosis. Although competing endogenous RNA (ceRNA) networks involving long non-coding RNAs (lncRNAs) have been proposed as key regulators of tumor progression, their cell type-specific roles in HGSOC remain unclear.

Objectives: We aimed to identify lncRNA-associated ceRNA networks active within the HGSOC tumor microenvironment.

Methods: We performed an integrative analysis combining single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq datasets. Cancer cells were isolated, and coexpression analyses were conducted using high-dimensional weighted gene coexpression network analysis. The resulting ceRNA modules were validated and functionally annotated using The Cancer Genome Atlas and pathway enrichment analysis.

Results: Our analysis identified a cancer cell-specific ceRNA network involving MIR100HG, mir-224-5p, and EYA4. Interaction prediction and expression correlation analyses indicated that MIR100HG may function as a molecular sponge for mir-224-5p, thereby alleviating its suppression of EYA4. The presence of a 7mer-m8 seed match between mir-224-5p and EYA4 supported this interaction. Pathway analysis suggested a link between the identified ceRNA network and the Wnt signaling pathway, a key driver of tumor initiation and metastasis.

Conclusion: The MIR100HG-mir-224-5p-EYA4 ceRNA network may promote tumor progression by modulating Wnt signaling. These findings offer insights into a potential posttranscriptional regulatory mechanism in tumor development and therapeutic targeting in HGSOC.

Urine-based liquid biopsy represents a transformative, non-invasive diagnostic approach that enables the molecular profiling of tumor-derived biomarkers shed into the urinary tract. By overcoming the limitations of traditional tissue biopsies, this methodology facilitates early cancer detection, real-time monitoring of therapeutic response, and longitudinal disease surveillance. This review provides a comprehensive overview of current urine-based liquid biopsy platforms, with a focus on protein and RNA biomarkers in urological cancers. We highlight the clinical relevance of these biomarkers and discuss technological innovations-including multi-omics integration, machine learning applications, and point-of-care testing-that are expanding their diagnostic utility. By leveraging the unique anatomical accessibility of urological malignancies via urine sampling, this field is poised to significantly enhance precision oncology.

Background: Cereblon (CRBN) serves as the substrate recognition subunit of the CRL4-CRBN E3 ubiquitin ligase complex and isthe primary target of immunomodulatory drugs (IMiDs) in cancer therapy. While CRBN mutations occur infrequently in cancer, reduced CRBN expression correlates with poor IMiD response and treatment resistance, suggesting nongeneticregulatory mechanisms may govern CRBN expression.

Objective: We investigated CRBN expression patterns across multiple cancer types and examined the role of promotermethylation in regulating CRBN expression and its clinical significance.

Methods: We analyzed CRBN expression patterns using GENT2 database analysis and examined CRBN methylation status indiverse human cancer cell lines using methylation-specific PCR (MSP) and bisulfite genomic sequencing. We analyzedthe clinical significance of CRBN methylation and expression using TCGA and GENT2 databases with Kaplan-Meiersurvival analyses.

Results: CRBN expression was significantly downregulated in breast, cervical, head and neck, lung, and skin cancers comparedto normal tissues. We identified a CpG island 1kb upstream of the CRBN transcriptional start site, with cancer celllines exhibiting partial methylation patterns. Bisulfite sequencing confirmed specific CpG methylation sites withinCRBN promoter regions. CRBN promoter hypermethylation significantly correlated with increased mortality risk inbreast, lung, acute myeloid leukemia, and bladder cancers, while low CRBN expression was associated with poorsurvival in breast, lung, brain, and ovarian cancers. Combined low expression and high methylation stronglypredicted poor outcomes in breast and lung cancers.

Conclusions: CRBN expression is partially regulated by promoter methylation in specific cancer types, with epigenetic silencingcontributing to treatment resistance and poor prognosis. CRBN methylation and expression serve as important pancancerprognostic biomarkers, highlighting the potential for epigenetic therapies to restore CRBN function andovercome therapeutic resistance.

Background: Cisplatin resistance significantly limits the effectiveness of chemotherapy in esophageal squamous cell carcinoma (ESCC). Understanding the molecular mechanisms driving resistance is essential for improving treatment outcomes.

Objective: This study aimed to investigate the role of the FOXK1/AKT2 axis in cisplatin resistance in ESCC cells and to evaluate the potential of triptonide in reversing this resistance.

Methods: Cisplatin sensitivity was assessed in ESCC cell lines with altered FOXK1 expression. A cisplatin-resistant TE1 cell line (TE1-R) was established by prolonged low-dose cisplatin exposure. Luciferase reporter assays were conducted to determine whether FOXK1 activates AKT2 transcription. Cell viability, colony formation, apoptosis assays, and expression analysis of apoptosis-related genes were performed to examine the effects of FOXK1, AKT2, and triptonide.

Results: FOXK1 overexpression reduced cisplatin sensitivity in ESCC cells, while FOXK1 knockdown restored sensitivity in TE1-R cells. FOXK1 directly enhanced AKT2 transcription by binding to its promoter region. The FOXK1/AKT2 axis promoted cell proliferation and suppressed cisplatin-induced apoptosis. Triptonide treatment downregulated FOXK1 and AKT2 expression, inhibited proliferation, induced apoptosis, and sensitized ESCC cells to cisplatin in a synergistic manner.

Conclusions: The FOXK1/AKT2 signaling axis contributes to cisplatin resistance in ESCC. Triptonide reverses resistance by inhibiting this axis, offering a promising strategy to enhance cisplatin efficacy in ESCC therapy.

Background: The high heterogeneity of basal-like breast cancer (BLBC) impedes early diagnosis and accurate prognosis. Beta-alanine, a non-essential amino acid involved in various metabolic pathways, accumulates in BLBC cells and may exacerbate tumor progression.

Objective: This study aimed to develop a prognostic model based on beta-alanine metabolism genes and investigate the clinical significance and therapeutic potential of EHHADH in BLBC.

Methods: We applied Least Absolute Shrinkage and Selection Operator regression to 22 beta-alanine metabolism genes to construct a prognostic model using transcriptomic data. Subsequent analyses included overall survival, mutation landscape, functional enrichment, drug sensitivity, and in vitro validation of EHHADH function. Structure-based virtual screening was conducted to identify potential EHHADH inhibitors.

Results: A beta-alanine metabolism-related prognostic signature was successfully developed. EHHADH was identified as a risk gene negatively associated with survival. High EHHADH expression correlated with increased sensitivity to chemotherapeutic agents, including docetaxel, doxorubicin, gemcitabine, paclitaxel, tamoxifen, and vinorelbine. Knockdown of EHHADH reduced BLBC cell proliferation and migration. Virtual screening revealed several candidate small molecules targeting EHHADH.

Conclusion: This study establishes a prognostic model based on beta-alanine metabolism in BLBC and identifies EHHADH as a potential biomarker and drug target, providing insights for precision therapy in metabolically reprogrammed breast cancer.

Background: Sexual dimorphism in insects arises from morphological, physiological, and behavioral differences that often reflect reproductive strategies. However, its molecular basis remains poorly understood in non-model and endangered species.

Objective: To elucidate the molecular mechanisms underlying sexual dimorphism in Callipogon relictus-a long-horned beetle of high conservation importance.

Methods: We conducted a transcriptome-wide analysis of sex-biased gene expression in pupal tissues of C. relictus. RNA sequencing was performed on six pupal tissues (mandible, maxillary palpus, foreleg, midleg, elytra, and hindwing) from both sexes. Differentially expressed genes were defined using an absolute log₂ fold change > 1 and raw p-value < 0.05. For enrichment analyses, Benjamini-Hochberg false discovery rate (FDR) correction was applied. Throughout the manuscript, p-value refers to unadjusted values, and FDR indicates corrected values. Functional annotation and Gene Ontology enrichment were performed using Drosophila melanogaster orthologs, and conserved sex-biased genes were identified.

Results: Overall, 2,913 sex-biased genes were detected in these tissues. Male tissues were enriched in cuticle formation, chitin metabolism, immune defense, and cell cycle regulation, consistent with the development of enlarged mandibles and reinforced cuticles. Female tissues were enriched in metabolic processes, hormone regulation, and muscle development, reflecting reproductive and flight-related investments. A conserved set of 33 male-biased and 14 female-biased genes was shared across tissues. The key male-biased genes were linked to juvenile hormone biosynthesis, chemosensory signaling, and cuticle reinforcement. The key female-biased genes are associated with oogenesis and hormonal metabolism.

Conclusion: These findings reveal the tissue-specific and conserved regulators of sexual dimorphism in C. relictus; they provide a foundation for functional studies and support conservation strategies, including captive rearing and sustainable management, for this endangered beetle.