Overexpression of Tobacco GCN2 Stimulates Multiple Physiological Changes Associated With Stress Tolerance.

General control non-derepressible-2 (GCN2) is a ubiquitous protein kinase that phosphorylates the α subunit of the eukaryotic initiation factor, eIF2, preventing the initiation of a new cycle of protein synthesis, subsequently reducing the global protein biosynthesis. GCN2 can also regulate the response of plants to biotic and abiotic stresses. In this study, two GCN2 homologs, NtGCN2-1 and NtGCN2-2, were cloned from Nicotiana tabacum, and were predicted to have been derived from their progenitors in N. tomentosiformis and N. sylvestris, respectively. The phosphorylation of NteIF2α could be activated by promoting the expression of NtGCN2 with plant hormones, including salicylic acid (SA), azelaic acid (AZA), methyl jasmonate (MeJA), and by imposition of different stresses (Bemisia tabaci infection, drought, and cold), indicating that NtGCN2 is involved in the response of plants to multiple biotic and abiotic stresses. We also observed that the overexpression of NtGCN2-1 significantly influenced different physiological processes. It promoted seed germination and root elongation. The content of total soluble sugars and reducing sugars were decreased, whereas those of chlorophyll a and b were increased in the GCN2 overexpressing plants. In addition, the overexpressing plants had lower content of reactive oxygen species and exhibited higher antioxidant activities. These physiological alterations could be attributed to the changes in the endogenous phytohormones, decrease in the SA and abscisic acid content, and accumulation of MeJA and AZA. It indicated that the overexpression of NtGCN2 in tobacco, stimulated the plant defense responses via phosphorylation of NteIF2α and regulation of plant hormones, and changes in the antioxidant ability and plant nutrient status.

Dipalmitoylphosphatidic acid inhibits tumor growth in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis, accounting for approximately 12-24% of breast cancer cases. Accumulating evidence has indicated that there is no effective targeted therapy available for TNBC. Dipalmitoylphosphatidic acid (DPPA) is a bioactive phospholipid. However, the function of DPPA in the growth of TNBC has not yet been studied. In this study, we employed TNBC cells and a subcutaneous tumor model to elucidate the possible effect of DPPA on tumor growth in TNBC. We showed that DPPA significantly inhibited tumor growth in the mouse subcutaneous tumor model and suppressed cell proliferation and angiogenesis in TNBC tumor tissues. This inhibition was mediated partly by suppressing the expression of cyclin B1 (CCNB1), which directly promoted the accumulation of cells in the G2 phase and arrested cell cycle progression in human TNBC. In addition, the inhibition of tumor growth by DPPA may also be mediated by the suppression of tumor angiogenesis in TNBC. This work provides initial evidence that DPPA might be vital as an anti-tumor drug to treat TNBC.

The VDR gene FokI polymorphism and ovarian cancer risk.

The polymorphism of vitamin D receptor (VDR) gene is demonstrated to affect the activity of its encoding protein and the subsequent downstream effects mediated by vitamin D. Mutations in VDR gene FokI have been suggested in the development of various cancers. Whether the polymorphism of the VDR gene FokI confers risk to ovarian cancer still remains controversial across the published studies in different ethnicity. The aim of this meta-analysis was to determine the role of VDR gene FokI variant in the susceptibility to ovarian cancer. Six publications with 14 individual case-control studies involving a total of 10,964 subjects were finally included into our study after a comprehensive literature search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association between the VDR gene FokI polymorphism and ovarian cancer risk was estimated under the allelic (T vs. C), homozygous (TT vs. CC), additive (CT vs. CC), recessive (TT vs. CC + CT), and dominant (CT + TT vs. CC) gene models. The overall odds ratios (ORs) for the contrast models of T vs. C, TT vs. CC, CT vs. CC, and CT + TT vs. CC indicated that the VDR gene FokI variant was related to an increased risk of ovarian cancer (OR(T vs. C) = 1.09, 95 % confidence interval (CI) 1.03-1.15, P(OR) = 0.004; OR(TT vs. CC) = 1.17, 95 % CI 1.04-1.32, P(OR) = 0.011; OR(CT vs. CC) = 1.10, 95 % CI 1.01-1.20, P(OR) = 0.027; OR(CT + TT vs. CC) = 1.12, 95 % CI 1.03-1.21, P(OR) = 0.007). The stratified analysis among the Caucasians also identified a significant association between the VDR gene FokI polymorphism and the susceptibility to ovarian cancer. The present meta-analysis with large available published data has revealed that the VDR gene FokI polymorphism confers susceptibility to ovarian cancer, particularly among the Caucasian population.

Complete chloroplast genome sequence of a tree fern Alsophila spinulosa: insights into evolutionary changes in fern chloroplast genomes.

BACKGROUND: Ferns have generally been neglected in studies of chloroplast genomics. Before this study, only one polypod and two basal ferns had their complete chloroplast (cp) genome reported. Tree ferns represent an ancient fern lineage that first occurred in the Late Triassic. In recent phylogenetic analyses, tree ferns were shown to be the sister group of polypods, the most diverse group of living ferns. Availability of cp genome sequence from a tree fern will facilitate interpretation of the evolutionary changes of fern cp genomes. Here we have sequenced the complete cp genome of a scaly tree fern Alsophila spinulosa (Cyatheaceae). RESULTS: The Alsophila cp genome is 156,661 base pairs (bp) in size, and has a typical quadripartite structure with the large (LSC, 86,308 bp) and small single copy (SSC, 21,623 bp) regions separated by two copies of an inverted repeat (IRs, 24,365 bp each). This genome contains 117 different genes encoding 85 proteins, 4 rRNAs and 28 tRNAs. Pseudogenes of ycf66 and trnT-UGU are also detected in this genome. A unique trnR-UCG gene (derived from trnR-CCG) is found between rbcL and accD. The Alsophila cp genome shares some unusual characteristics with the previously sequenced cp genome of the polypod fern Adiantum capillus-veneris, including the absence of 5 tRNA genes that exist in most other cp genomes. The genome shows a high degree of synteny with that of Adiantum, but differs considerably from two basal ferns (Angiopteris evecta and Psilotum nudum). At one endpoint of an ancient inversion we detected a highly repeated 565-bp-region that is absent from the Adiantum cp genome. An additional minor inversion of the trnD-GUC, which is possibly shared by all ferns, was identified by comparison between the fern and other land plant cp genomes. CONCLUSION: By comparing four fern cp genome sequences it was confirmed that two major rearrangements distinguish higher leptosporangiate ferns from basal fern lineages. The Alsophila cp genome is very similar to that of the polypod fern Adiantum in terms of gene content, gene order and GC content. However, there exist some striking differences between them: the trnR-UCG gene represents a putative molecular apomorphy of tree ferns; and the repeats observed at one inversion endpoint may be a vestige of some unknown rearrangement(s). This work provided fresh insights into the fern cp genome evolution as well as useful data for future phylogenetic studies.