Biological Research最新文献

Background: Polyploidization is associated with progression of cancer, making cancer cells more dangerous. The common polyploid cancer cells constitute a considerable part of tumors (up to 56% in metastases). The giant polyploid cancer cells (PGCC), which appear under severe stress caused by treatment when the majority of cells die, present an enigmatic phenomenon both in fundamental and practical sense because they develop treatment resistance.

Results: Using transcriptome meta-analysis, we studied different types of polyploid cancer cells and found that in common polyploid cancer cells, the genes of unicellular (UC) origin and stemness are upregulated (compared to diploid cancer cells). At that, the upregulated UC genes show a higher local and global protein interactome centrality than the upregulated stemness genes, suggesting that the UC interactome attractor is a driving force behind this backward movement along the evodevo axis. Surprisingly, PGCC show the opposite picture. There occurs the suppression of UC and stemness genes with the upregulation of multicellular genes (especially those involved in intercellular communication), suggesting a reversal towards multicellular (MC) state. This effect is enhanced in PGCC's early progeny but diminished in the late progeny, indicating its transient nature. PGCC of different origin (breast, ovarian, prostate cancers), induced by different stresses (radiation or drugs with various mechanisms of action), show a similar behavior. The first principal component of transcriptome profiles, which is common for all cell types (initial cancer cells, PGCC, early and late progeny) and contains the major part of expression variance, is also directed along the gene evolutionary age axis.

Conclusions: While the common polyploid cancer cells comply with the 'serial atavism' model of oncogenesis, PGCC present a unique phenomenon of the short-term return to multicellularity probably associated with collective acquisition of resistance to treatment. Our analysis revealed also the evolutionary origin of the main differences in gene expression, emphasizing the importance of gene age axis in transcriptome analyses. The deep evolutionary basis of variation in gene expression across and within cell types might become a general framework for interrelated problems of cell and cancer biology and regenerative medicine.

Background: Protein kinase CK2 is known to exist as a tetramer of two catalytic α- or α'- subunits and two non-catalytic β-subunits, or as multimers of this tetramer. Moreover, CK2α (CSNK2A1) and CK2α' (CSNK2A2) are also active in the absence of CK2β (CSNK2B). Very little is known about specific functions of the individual subunits of protein kinase CK2.

Results: In order to study the effects of CK2α and CK2α' on gene expression, we used the Mus musculus pancreatic α-cell line αTC1 and two derivatives with either CK2α (KO1 cells) or CK2α' (KO2 cells) expression knocked-out by CRISPR/Cas technology. We found numerous genes deregulated in both KO1 and KO2 cells compared to the parental cells. Applying stringent thresholds, 266 genes were found down-regulated and 153 genes up-regulated in KO1 cells, 233 genes were found down-regulated and 84 genes up-regulated in KO2 cells. Dozens of genes were found deregulated in a similar fashion in both KO1 and KO2 cells. We found altered expression of genes involved in the differentiation of pancreatic cells, including Hox genes, and in the regulation of glucagon synthesis or secretion. Moreover, many of the deregulated genes play an important role in developmental processes and in neuronal cell biology.

Conclusion: Our findings reveal individual and shared functions of the CK2α and CK2α' catalytic subunits, in particular regarding their involvement in regulating gene expression.

Methionine serves as an essential amino acid regulating de novo protein synthesis and redox homeostasis. Previous studies have established adverse impacts of methionine restriction and deprivation on semen quality, but effects on early spermatogenesis remain poorly characterized. In this study, a methionine dietary model (0.86%, 0.17%, 0%) was used to investigate the role of methionine in early spermatogenesis. The results indicated that methionine deprivation caused spermatogenesis defects by inhibiting spermatogonial proliferation and increasing apoptosis. Further studies showed that methionine deprivation downregulated mitochondrial function-related genes (Gpx4, Fis1 and Gstm1), but upregulated ISR- (Atf4, Chac1 and Ddit3) and DNA damage response-related genes (Cdkn1a, Chek2 and Atm). Meanwhile, methionine deprivation caused mitochondrial dysfunction characterized by mitochondrial membrane potential depolarization, ROS accumulation, and MitoSOX accumulation. Methionine deprivation also caused an obvious increase in DNA damage response proteins (γH2AX, p-CHK2 and p-p53) and pro-apoptotic proteins (PUMA, BAX and c-PARP1), but suppressed anti-apoptotic protein BCL2. Furthermore, NAC effectively reversed the proliferation deficiency of GC-1 cells caused by methionine deprivation. Collectively, these findings suggest that methionine deprivation triggers ISR activation, which subsequently induces spermatogonial apoptosis via oxidative stress and the CHK2-p53/p21 signaling cascade. This study highlights the critical role of methionine in early spermatogenesis, provides mechanistic insights for optimizing dietary interventions and addresses related reproductive disorders.

NR6A1 is a member of the nuclear receptor superfamily of ligand-activated transcription factors and can bind to conserved DNA sequences, acting as a transcriptional repressor. NR6A1 has been reported to promote prostate cancer, gastric cancer, and testicular germ cell tumor progression. In the present study, we confirmed the oncogenic role of NR6A1 in several types of cancer cells, including HeLa, TFK1, and A549 cells, and revealed that NR6A1 knockdown led to a decrease in lung adenocarcinoma cell proliferation, a reduction in glucose consumption, a reduction in lactic acid production, and decreases in ATP levels and mitochondrial membrane potential. Mechanistically, through a series of methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RT-qPCR, Western blot analysis, and functional rescue experiments, we demonstrated that NR6A1 may promote the expression of HK1 by directly suppressing miR-302a, thereby reprogramming tumor cell glycolysis and enhancing lung adenocarcinoma cell growth. In addition, we found that NR6A1 can affect mTOR signaling, suggesting a broader role in tumor metabolism regulation. In summary, our data indicate that NR6A1 plays an oncogenic role by reprogramming glycolysis via the miR-302a/HK1 axis in lung adenocarcinoma.

Seed coat color is crucial for consumer preference in soybeans. This study explores the genetic mechanisms underlying yellow, green, and brown seed coats through reciprocal crosses, revealing that seed coat color is maternally inherited, with F₁ seeds matching the female parental phenotype. In the F₂ generation, all seeds had green coats, while F₃ segregation patterns followed a two-gene epistatic model. The yellow (SKAF148) x brown (AGS457) cross segregated in a 9:3:4 ratio (green: yellow: brown), while yellow x green (SKAF148 x AGS346) segregated in a 3:1 ratio (green: yellow). Here, we report that two loci, G1 and G2, govern color expression. Dominant alleles at both loci (G1_G2_) produced green seed coats, while yellow required G1_g2g2 and brown required homozygous recessive g1g1 alleles, demonstrating recessive epistasis where g1g1 masked G2 effects. This research establishes a genetic pathway from brown to yellow to green, offering key insights into the digenic inheritance of seed coat color. The parental genotypes were inferred as G1G1g2g2 (yellow), G1G1G2G2 (green), and g1g1G2G2 (brown). These findings provide valuable guidance for breeding programs targeting consumer-preferred seed coat colors in soybeans.

Background: Botrytis cinerea is a phytopathogenic fungus responsible for gray mold disease in a wide range of hosts, including ornamentals, vegetables, and fruit-bearing plants. Similarly, Cryphonectria parasitica infects the American chestnut, causing a lethal condition known as chestnut blight. From this species, the CHV1-EP713 virus, classified as a hypovirus due to its ability to reduce fungal virulence, has been isolated and characterized. Building on this knowledge, we aimed to express the full-length cDNA of CHV1-EP713 in B. cinerea to asess whether its expression could alter the fungal phenotype.

Results: To achieve the expression of the hypovirus cDNA in B. cinerea, the pXH9 vector encoding the CHV1-EP713 cDNA and the p18 plasmid containing the Agrobacterium tumefaciens Ti plasmid T-DNA region were fused to generate the p18-XH9 construct. Transformation of the virulent B. cinerea strain CCg55L with A. tumefaciens carrying this construct yielded hygromycin B-resistant transformants. Nucleic acid analysis revealed a ~ 13-kbp double-stranded RNA, consistent with a replicative intermediate of the viral genome. PCR and RT-PCR confirmed integration and expression of the viral cDNA, supporting the establishment of a productive mycoviral infection. Phenotypically, transformants showed reduced radial growth and sporulation compared to the parental strain. Moreover, grapevine leaf infection assays revealed significantly reduced tissue damage and distinct oxidative responses, indicating a reduction in virulence.

Conclusion: Together, these results demonstrate that transformation of a virulent B. cinerea strain with CHV1-EP713 cDNA can lead to phenotypic changes consistent with hypovirulence. The observed alterations in growth, sporulation, and pathogenicity are likely linked to viral expression and/or replication, highlighting the potential of hypoviruses as biological control agents against phytopathogenic fungi.