Genes & genomics最新文献

Background: Human endogenous retroviruses (HERVs) were integrated into the human genome millions of years ago and have since proliferated to comprise about 8% of the human genome. For a long time, HERVs were thought to be remnants of ancient viruses, rendered inactive over the ages. However, recent studies have revealed that HERVs are involved in various diseases, including cancer. Notably, HERVs have been found to play a crucial role in immune responses and inflammatory processes, indicating their significant influence on the regulation of immune-related diseases.

Objective: We reported in previous reports that HERV-K119 env Knockout (KO) and inflammatory response were associated. In this study, we identified the correlation between inflammatory disease and HERV-K Env and TNF-Alpha protein expression in multiple types of colon disease tissue and lung disease spectrum tissue.

Methods: We performed Immunofluorescence (IF) using multiple types of colon disease and lung disease spectrum tissue microarray (TMAs) and compared and analyzed the patient clinical data provided.

Results: As a result, we identified that the expression of HERV-K Env and TNF-Alpha proteins in certain colorectal inflammatory diseases and certain lung inflammatory diseases showed specific expression. And through the analysis of the clinical data provided, environmental factors could be identified.

Conclusion: Our study demonstrates that the relationship between TNF-Alpha and HERV-K Env expression in inflammation disease and clinical significance of disease tissues.

Background: Clear cell renal cell carcinoma (ccRCC) represents a common renal carcinoma subtype influenced by the immune microenvironment. LIM and SH3 Protein 2 (LASP2), an actin-binding protein within the nebulin family, contributes to cellular immunity and adhesion mechanisms.

Objective: This study aimed to clarify the immunological and prognostic relevance of LASP2 in ccRCC.

Methods: Using clinical and expression data from TCGA, LASP2 expression levels were analyzed alongside clinicopathological features in ccRCC patients. Validation was conducted through real-world samples and tissue microarrays. Comprehensive analysis using online databases examined genetic mutations, DNA methylation patterns, and immune microenvironment characteristics. Gene set enrichment analysis (GSEA) provided insights into LASP2's potential mechanisms in ccRCC.

Results: LASP2 expression was notably reduced and correlated with adverse clinicopathological features and prognosis in ccRCC patients. Prognostic associations were identified across multiple CpG DNA methylation sites. LASP2 levels showed significant correlations with immune cell infiltration and checkpoint genes, including PDCD1 and CTLA4. GSEA findings highlighted LASP2's enrichment within metabolic pathways and signaling networks, such as fatty acid metabolism, TGF-β signaling, and epithelial-mesenchymal transition.

Conclusion: LASP2 emerged as an immune-associated biomarker linked to poorer survival outcomes in ccRCC, suggesting its potential as a novel anti-cancer target and prognostic indicator in ccRCC.

Background: Vegetable oils are primarily composed of unsaturated fatty acids. Soybean [Glycine max (L.) Merr.] oil, accounting for 28% of the global production of vegetable oil, contains mainly two saturated fatty acids (palmitic acid and stearic acid) and three unsaturated fatty acids (oleic acid, linoleic acid, and linolenic acid) in seeds.

Objective: The five fatty acids determine soybean oil quality. We aimed to identify genetic relationship between genomics and fatty acid contents in soybean mutant pool.

Methods: This study used a mutant diversity pool (MDP) comprising 192 soybean lines. A genome-wide association study (GWAS) was conducted with the diverse fatty acid contents in MDP and 17,631 filtered SNPs from genotyping-by-sequencing (GBS).

Results: The GWAS revealed nine significant SNPs within intragenic regions that were associated with fatty acid composition. These SNPs corresponded to six genes (Glyma.03g042500, Glyma.07g069200, Glyma.13g150200, Glyma.14g223100, Glyma.15g084700, and Glyma.15g274000), of which three (Glyma.03g042500, Glyma.13g150200, and Glyma.15g274000) were predicted to be candidate genes influencing oleic acid, linoleic acid, and linolenic acid contents. Analyses of SNP allelic effects revealed the largest and smallest significant differences in fatty acid contents were 5.53% (linolenic acid) and 0.4% (stearic acid), respectively.

Conclusion: The present study detected significant phenotypic variations and genetic associations underlying the fatty acid composition of soybean seeds in MDP lines. The mutant seeds differed from the original cultivars in terms of fatty acids composition, with the allelic effects of significant SNPs influencing the fatty acid content in seeds. These findings may be useful for enhancing breeding strategies to optimize soybean oil quality for various uses.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, drug resistance limits their efficacy. Cytoskeleton-associated protein 4 (CKAP4) has been linked to cancer progression, but its role in EGFR-TKI resistance remains unclear.

Objective: This study investigates the clinical relevance of CKAP4 as a therapeutic target to overcome EGFR-TKI resistance in lung adenocarcinoma (LUAD) patients.

Methods: GEO datasets were analyzed to identify 24 differentially expressed genes associated with EGFR-TKI resistance, with CKAP4 selected via functional annotation and scoring using the VarElect tool. The prognostic significance of CKAP4 was evaluated using public databases, and its upregulation was confirmed in osimertinib-tolerant H1975 cells through quantitative reverse transcription-polymerase chain reaction.

Results: Integrated bioinformatics analysis identified CKAP4 as strongly associated with EGFR-TKI resistance. Elevated CKAP4 expression was particularly linked to poorer clinical outcomes in LUAD patients. Notably, osimertinib-tolerant cells exhibited high CKAP4 expression, correlating positively with increased half-maximal inhibitory concentrations of EGFR-TKIs. LUAD patients with upregulated CKAP4 showed significantly reduced overall and relapse-free survival.

Conclusion: This study underscores the prognostic value of CKAP4 in EGFR-mutated LUAD and highlights its potential as a therapeutic target to counter EGFR-TKI resistance.

Background: The mechanical remodeling of tumor microenvironment is critical for non-small cell lung cancer (NSCLC) progression. Dual-specificity phosphatase 23 (DUSP23) has been previously identified as a mechano-responsive gene, but its role in NSCLC progression remains unknown.

Objective: We aim to elucidate the clinical significance of DUSP23 in NSCLC progression.

Methods: We analyzed the expression of DUSP23 in cancer using polyacrylamide hydrogels designed to mimic the stiffness of normal (soft; ~0.5 kPa) and cancerous (stiff; ~40 kPa) tissues. The prognostic significance of DUSP23 expression in patients was examined using public databases. Additionally, we conducted various cell-based assays and transcriptomic analyses in DUSP23-silenced NSCLC cell lines. A risk score prognosis model was constructed using univariate Cox regression and Kaplan-Meier analysis.

Results: Our findings show that DUSP23 is upregulated in stiff matrices and is highly associated with poor prognosis in patients with solid cancers such as NSCLC and breast cancer. Silencing of DUSP23 resulted in decreased cell proliferation and invasion. Transcriptomic profiling revealed that 182 genes were downregulated, and 230 genes upregulated following DUSP23-depletion. Notably, 182 downregulated genes were enriched in cancer-related pathways, including cell cycle progression and cytoskeleton organization. Through KEGG pathway analysis, we identified 11 cancer-related genes and developed a prognostic risk model. In this model, the high-risk group of NSCLC patients exhibited significantly shorter overall survival compared to low-risk group, based on public datasets.

Conclusion: Our study demonstrates the clinical significance of DUSP23 as a prognostic marker in NSCLC and highlights its potential role of DUSP23 in promoting NSCLC progression.

Background: Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved.

Objective: In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis.

Methods: To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays.

Results: Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells.

Conclusions: The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.

Background: The Wnt gene family plays pivotal roles in a variety of biological processes including cell proliferation and differentiation, apoptosis, and embryonic development. Identifying the Wnt signaling pathway in abalone could provide a basis for elucidating growth and development mechanisms and improving quality.

Objective: To identify the number, protein physicochemical properties, gene structure, phylogenetic analysis, and expression profiles of the Wnt gene family in abalone.

Methods: A comprehensive genome-wide analysis was performed to identify the Wnt gene family in the genomes of three abalone species (Haliotis discus hannai, H. rubra, and H. rufescens).

Results: Ten single-copy Wnt genes were identified in each abalone species, suggesting that the number of Wnt genes was relatively conserved in Haliotis. Eight Wnt gene subfamilies, including Wnt1, Wnt4, Wnt5, Wnt6, Wnt7, Wnt10, Wnt16, and WntA, are present in all three species. Each abalone species contains two species-specific subfamilies (Wnt9 and Wnt11 in H. discus hannai, Wnt2 and Wnt11 in H. rubra, and Wnt2 and Wnt9 in H. rufescens), reflecting polymorphisms of the Wnt genes in Haliotis. Interestingly, gastropods are characterised by the loss of Wnt8, suggesting a potential evolutionary specificity in gastropods. As expected, Wnt3 is absent in all protostomes, including the abalone. In addition, spatio-temporal expression profiling revealed differential expression levels of the Wnt genes at different developmental stages and in different tissues of H. discus hannai. HdWnt5 and HdWntA might participate in several processes during larval development stages, including germ layer formation and body axis elongation. HdWnt5 may be involved in eye and tentacle development. HdWnt10 may be related to muscle development, and HdWnt6 may be involved in shell formation in abalone.

Conclusion: To our knowledge, the results of this study, which is the first genome-wide investigation of the Wnt gene family in abalone, lay the groundwork for future research on the evolution and function of the Wnt gene family in Gastropoda.

Background: Retinitis pigmentosa (RP) is a genetically heterogeneous disease. RP 79 has been associated with heterozygous variants of hexokinase 1 (HK1). Only two missense HK1 variants have been reported in 11 families.

Objective: To discover the molecular pathogenic mechanism of RP and validate the biological harm of HK1 through in vitro experiments.

Methods: We conducted a genetic analysis of a 3-year-old female patient with RP and her family. We also evaluated the ocular phenotypes caused by HK1 (the identified variant). Peripheral blood samples were collected from the patient, her parents, and her brother, and trio whole-exome sequencing was performed. A protein structure analysis was performed to assess the functional impact of the variant, and a mutant plasmid was constructed for the quantitative polymerase chain reaction (qPCR) and western blot (WB) analysis of the effects of the variant on transcription and protein translation.

Results: The patient harbored the NM_000188.3: c.613del (p.Ala205Leufs*3) variant, which is a heterozygous variant of HK1. Sanger sequencing confirmed the presence of this variant in the patient; however, the patient's parents and brother had the wild-type variant. The protein structure analysis indicated that the variant resulted in a truncated protein caused by premature termination of amino acid coding. The qPCR results indicated that the variant may not have affected the transcription process. However, the WB analysis demonstrated that the mutant HK-1 protein was not expressed and that the wild-type group exhibited normal expression.

Conclusions: Our patient had a loss-of-function (LoF) variant of HK1, which may be the genetic cause of typical features of RP that are observed at an early age. These findings expand the spectrum of HK1 variants and phenotypes and suggest that LoF variants of HK1 may represent a specific pathogenic mechanism of RP.

Background: Mesorhabditis is known for its somatic genome being only a small portion of the germline genome due to programmed DNA elimination. This phenotype may be associated with the maintenance of telomeres at the ends of fragmented somatic chromosomes.

Objective: To comprehensively investigate the telomeric regions of Mesorhabditis nematodes at the sequence level, we endeavored to collect a Mesorhabditis nematode in the Republic of Korea and acquire its highly contiguous genome sequences.

Methods: We isolated a Mesorhabditis nematode and assembled its 108-Mb draft genome using both 6.3 Gb (53 ×) of short-read and 3.0 Gb (25 × , N50 = 5.7 kb) of nanopore-based long-read sequencing data. Our genome assembly exhibits comparable quality to the public genome of Mesorhabditis belari in terms of contiguity and evolutionary conserved genes.

Results: Unexpectedly, our Mesorhabditis genome has many more interstitial telomeric sequences (ITSs), specifically subtelomeric ones, compared to the genomes of Caenorhabditis elegans and M. belari. Moreover, several subtelomeric sequences containing ITSs had 4-26 homologous sequences, implying they are highly repetitive. Based on this highly repetitive nature, we hypothesize that subtelomeric ITSs might have accumulated through the action of transposable elements containing ITSs.

Conclusions: It still remains elusive whether these ITS-containing units are associated with programmed DNA elimination, but they may facilitate new telomere formation after DNA elimination. Our genomic resources for Mesorhabditis can aid in understanding how its distinct phenotypes have evolved.

Background: Prostate cancer (PCa) is a serious malignancy. The main causes of PCa aggravation and death are unexplained resistance to chemotherapy and bone metastases.

Objective: This study aimed to investigate the molecular mechanisms associated with the dynamic processes of progression, bone metastasis, and chemoresistance in PCa.

Methods: Through comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data, Gene Expression Omnibus (GEO) tumor progression and metastasis-related genes were identified. These genes were subjected to lasso regression modeling using the Cancer Genome Atlas (TCGA) database. Tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR (RT-qPCR) were used to evaluate osteoclast differentiation. CellMiner was used to confirm the effect of LDHA on chemoresistance. Finally, the relationship between LDHA and chemoresistance was verified using doxorubicin-resistant PCa cell lines.

Results: 7928 genes were identified as genes related to tumor progression and metastasis. Of these, 7 genes were found to be associated with PCa prognosis. The scRNA-seq and TCGA data showed that the expression of LDHA was higher in tumors and associated with poor prognosis of PCa. In addition, upregulation of LDHA in PCa cells induces osteoclast differentiation. Additionally, high LDHA expression was associated with resistance to Epirubicin, Elliptinium acetate, and doxorubicin. Cellular experiments demonstrated that LDHA knockdown inhibited doxorubicin resistance in PCa cells.

Conclusions: LDHA may play a potential contributory role in PCa initiation and development, bone metastasis, and chemoresistance. LDHA is a key target for the treatment of PCa.