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1.
Med Oncol ; 38(11): 132, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581882

RESUMO

WAC is closely related to the occurrence and development of tumors. However, its role in human glioblastoma (GBM) and its potential regulatory mechanisms have not been investigated. This study demonstrated that WAC is downregulated in GBM, and its low expression predicts a poor prognosis. We investigated the effect of WAC on the proliferation of glioma cells through a CCK-8 assay, EdU incorporation, and cell formation. The effects of WAC on apoptosis and autophagy in glioma were determined by flow cytometry, TUNEL detection, immunofluorescence, q-PCR, WB, and scanning electron microscopy. We found that overexpression of WAC inhibited the proliferation of glioma cells, promoted apoptosis, and induced autophagy. Therefore, WAC is likely to play a role as a new regulatory molecule in glioma.

2.
Nat Commun ; 12(1): 5445, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521854

RESUMO

Soybean (Glycine max) serves as a major source of protein and edible oils worldwide. The genetic and genomic bases of the adaptation of soybean to tropical regions remain largely unclear. Here, we identify the novel locus Time of Flowering 16 (Tof16), which confers delay flowering and improve yield at low latitudes and determines that it harbors the soybean homolog of LATE ELONGATED HYPOCOTYL (LHY). Tof16 and the previously identified J locus genetically additively but independently control yield under short-day conditions. More than 80% accessions in low latitude harbor the mutations of tof16 and j, which suggests that loss of functions of Tof16 and J are the major genetic basis of soybean adaptation into tropics. We suggest that maturity and yield traits can be quantitatively improved by modulating the genetic complexity of various alleles of the LHY homologs, J and E1. Our findings uncover the adaptation trajectory of soybean from its temperate origin to the tropics.


Assuntos
Adaptação Fisiológica/genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Soja/genética , Produtos Agrícolas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Flores/crescimento & desenvolvimento , Flores/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genoma de Planta , Fotoperíodo , Proteínas de Plantas/metabolismo , Locos de Características Quantitativas , Característica Quantitativa Herdável , Análise de Sequência de DNA , Soja/crescimento & desenvolvimento , Soja/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Clima Tropical
3.
Plant Biotechnol J ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388296

RESUMO

Soybean is one of the most important oilseed and fodder crops. Benefiting from the efforts of soybean breeders and the development of breeding technology, large number of germplasm has been generated over the last 100 years. Nevertheless, soybean breeding needs to be accelerated to meet the needs of a growing world population, to promote sustainable agriculture and to address future environmental changes. The acceleration is highly reliant on the discoveries in gene functional studies. The release of the reference soybean genome in 2010 has significantly facilitated the advance in soybean functional genomics. Here, we review the research progress in soybean omics (genomics, transcriptomics, epigenomics and proteomics), germplasm development (germplasm resources and databases), gene discovery (genes that are responsible for important soybean traits including yield, flowering and maturity, seed quality, stress resistance, nodulation and domestication) and transformation technology during the past decade. At the end, we also briefly discuss current challenges and future directions.

4.
Front Pharmacol ; 12: 659511, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381355

RESUMO

The most common primary central nervous system tumor in adults is glioblastoma multiforme (GBM). The high invasiveness of GBM cells is an important factor leading to inevitable tumor recurrence and a poor prognosis of patients. GNE-477, a novel PI3K/mTOR inhibitor, has been reported to exert antiproliferative effects on other cancer cells. However, researchers have not clearly determined whether GNE-477 produces antitumor effects on GBM. In the present study, GNE-477 significantly inhibited the proliferation, migration and invasion of U87 and U251 cells. In addition, GNE-477 also induced apoptosis of GBM cells, arresting the cell cycle in G0/G1 phase. More importantly, GNE-477 also reduced the levels of AKT and mTOR phosphorylation in the AKT/mTOR signaling pathway in a concentration-dependent manner. An increase in AKT activity induced by SC79 rescued the GNE-477-mediated inhibition of GBM cell proliferation and apoptosis. The antitumor effects of GNE-477 and the regulatory effects on related molecules were further confirmed in vivo using a nude mouse intracranial xenograft model. In conclusion, our study indicated that GNE-477 exerted significant antitumor effects on GBM cells in vitro and in vivo by downregulating the AKT/mTOR pathway.

5.
Curr Biol ; 31(17): 3755-3767.e4, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34270946

RESUMO

The classical soybean (Glycine max) trait long juvenile (LJ) is essentially a reduction in sensitivity to short-day (SD) conditions for induction and completion of flowering, and has been introduced into soybean cultivars to improve yield in tropical environments. However, only one locus, J, is known to confer LJ in low-latitude varieties. Here, we defined two quantitative trait loci contributing to the LJ trait, LJ16.1 and LJ16.2, and identified them as the florigen (FT) homologs FT2a and FT5a, respectively. The two selected florigen variations both delay flowering time under SD conditions by repressing the floral meristem identity gene GmAPETALA1. Single mutants have a relatively subtle effect on flowering time and displayed a substantial genetic compensation response, but this was absent in ft2a ft5a double mutants, which showed an enhanced LJ phenotype that translated to higher yields under SD conditions. A survey of sequence diversity suggests that FT2a and FT5a variants have diverse origins and have played distinct roles as soybean spread to lower latitudes. Our results show that integration of variants in the florigen genes offers a strategy for customizing flowering time to adjust adaptation and improve crop productivity in tropical regions.

6.
Sci China Life Sci ; 64(9): 1533-1545, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236584

RESUMO

Male sterility is an essential trait in hybrid seed production, especially for monoclinous and autogamous food crops. Soybean male-sterile ms1 mutant has been known for more than 50 years and could be instrumental in making hybrid seeds. However, the gene responsible for the male-sterile phenotype has remained unknown. Here, we report the map-based cloning and characterization of the MS1 gene in soybean. MS1 encodes a kinesin protein and localizes to the nucleus, where it is required for the male meiotic cytokinesis after telophase II. We further substantiated that MS1 colocalizes with microtubules and is essential for cell plate formation in soybean male gametogenesis through immunostaining. Both ms1 and CRISPR/Cas9 knockout mutants show complete male sterility but are otherwise phenotypically normal, making them perfect tools for producing hybrid seeds. The identification of MS1 has the practical potential for assembling the sterility system and speeding up hybrid soybean breeding.

7.
8.
ACS Omega ; 6(17): 11466-11473, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34056302

RESUMO

Glioblastoma (GBM) is the most common malignant tumor, and it is characterized by high cellular proliferation and invasion in the central nervous system of adults. Due to its high degree of heterogeneity and mortality, there is no effective therapy for GBM. In our study, we investigated the effect of the p38-MAPK signaling pathway inhibitor BIRB796 on GBM cells. Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EDU) staining, and cell cycle distribution analysis were performed, and the results showed that BIRB796 decreased proliferation in U87 and U251 cells. Moreover, wound healing and invasion assays were performed, which showed that BIRB796 inhibited the migration and invasion of human GBM cells. We found that BIRB796 treatment significantly decreased the formation of the cytoskeleton and thus downregulated the movement ability of the cells, as shown by phalloidin staining and vimentin immunofluorescence staining. Real-time polymerase chain reaction showed that the mRNA levels of MMP-2, Vimentin, CyclinD1, and Snail-1 were downregulated. Consistently, the expressions of MMP-2, Vimentin, CyclinD1, and p-p38 were also decreased after BIRB796 treatment. Taken together, all our results demonstrated that BIRB796 could play an antitumor role by inhibiting the proliferation and invasion in GBM cells. Thus, BIRB796 may be used as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment.

9.
J Cancer ; 12(10): 2912-2920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854592

RESUMO

Background: ADPRH is a modulator of CD8+ T cell functions, and dysregulation of ADPRH has been identified to involve in carcinogenesis of cancers. However, the association of ADPRH with low grade glioma (LGG) remains unclear. Methods: The expression of ADPRH in LGG was first analyzed in GLIOVIS and GEPIA databases and then validated by real-time PCR (rt-PCR), immunochemistry and human protein atlas (HPA). Univariate and multivariate Cox analysis and Kaplan-Meier plots were designed to assess the prognostic value of ADPRH in LGG. The correlation of ADPRH and immune infiltration was evaluated by data in TIMER and ESTIMATE databases. Gene set enrichment analysis was conducted to detect biological processes associated with ADPRH. Results: ADPRH was significantly upregulated in LGG in comparison to non-tumor brain samples in transcriptomic and proteomic levels. The high ADPRH expression indicated unfavorable overall survival (OS) and progression-free survival (PFS) in patients with LGG using Kaplan-Meier plots. And multivariate Cox analysis demonstrated the expression level of ADPRH was an independent prognosis-predicting index for OS and PFS of LGG patients in all cohorts separately. Gene Set Enrichment Analysis (GSEA) indicated that high expression of ADPRH was involved in the upregulation of P53 signaling pathway, KRAS signaling pathway, IL6/JAK-STAT3 signaling and TNF-beta signaling pathways. By TIMER and ESTIMATE databases, we identified ADPRH expression had strong correlation with tumor immune infiltrating cells (TIICs). Conclusions: In summary, our findings demonstrated that ADPRH might be a potential prognostic biomarker and correlated with TIICs in LGG.

10.
J Cancer ; 12(9): 2756-2767, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854635

RESUMO

Serum amyloid A1 (SAA1) is an inflammatory associated high-density lipoprotein. And It is also considered as a predictor and prognostic marker of cancer risk. However, its role and mechanisms in glioblastoma (GBM) still unclear. In this study, we validate that SAA1 is up-regulated in GBM, and its high expression predicts poor prognosis. SAA1 knockdown promotes the apoptosis of GBM cell. Mechanistically, SAA1 knockdown can inhibit serine/threonine protein kinase B (AKT) phosphorylation, thereby regulating the expression of apoptosis-related proteins such as Bcl2 and Bax, leading to GBM cell death. Moreover, Gliomas with low SAA1 expression have increased sensitivity to Temozolomide (TMZ). Low SAA1 expression segregated glioma patients who were treated with Temozolomide (TMZ) or with high MGMT promoter methylation into survival groups in TCGA and CGGA dataset. Our study strongly suggested that SAA1 was a regulator of cells apoptosis and acted not only as a prognostic marker but also a novel biomarker of sensitivity of glioma to TMZ.

11.
Pathol Res Pract ; 222: 153433, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33862563

RESUMO

Increasing literature reported that circRNAs play vital roles in the occurrence and progression of GBM and regulate GBM cell proliferation, metastases, and chemosensitivity. However, the expression pattern and function of circRNAs in GBM still need further studies. In our work, hsa_circ_0072309 was remarkably downregulated in GBM. Hsa_circ_0072309 inhibits proliferation and invasion of glioblastoma and affects cytoskeletal of GBM cells. Moreover, we found that the function of hsa_circ_0,072,309 in GBM was associated with HSP27, which was reported to be an important regulator of cell proliferation, invasion and cytoskeletal. Our study provides a novel view of hsa_circ_0072309 in GBM cell proliferation and invasion, indicating that hsa_circ_0072309 may act as a potential therapeutic target for GBM comprehensive treatment.

12.
Front Plant Sci ; 12: 649634, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897737

RESUMO

Transcription is the first step of central dogma, in which the genetic information stored in DNA is copied into RNA. In addition to mature RNA sequencing (RNA-seq), high-throughput nascent RNA assays have been established and applied to provide detailed transcriptional information. Here, we present the profiling of nascent RNA from trifoliate leaves and shoot apices of soybean. In combination with nascent RNA (chromatin-bound RNA, CB RNA) and RNA-seq, we found that introns were largely spliced cotranscriptionally. Although alternative splicing (AS) was mainly determined at nascent RNA biogenesis, differential AS between the leaf and shoot apex at the mature RNA level did not correlate well with cotranscriptional differential AS. Overall, RNA abundance was moderately correlated between nascent RNA and mature RNA within each tissue, but the fold changes between the leaf and shoot apex were highly correlated. Thousands of novel transcripts (mainly non-coding RNA) were detected by CB RNA-seq, including the overlap of natural antisense RNA with two important genes controlling soybean reproductive development, FT2a and Dt1. Taken together, we demonstrated the adoption of CB RNA-seq in soybean, which may shed light on gene expression regulation of important agronomic traits in leguminous crops.

13.
Front Oncol ; 11: 607150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777749

RESUMO

Liquid biopsy has entered clinical applications for several cancers, including metastatic breast, prostate, and colorectal cancer for CTC enumeration and NSCLC for EGFR mutations in ctDNA, and has improved the individualized treatment of many cancers, but relatively little progress has been made in validating circulating biomarkers for brain malignancies. So far, data on circulating tumor cells about glioma are limited, the application of circulating tumor cells as biomarker for glioma patients has only just begun. This article reviews the research status and application prospects of circulating tumor cells in gliomas. Several detection methods and research results of circulating tumor cells about clinical research in gliomas are briefly discussed. The wide application prospect of circulating tumor cells in glioma deserves further exploration, and the research on more sensitive and convenient detection methods is necessary.

14.
BMC Cancer ; 21(1): 251, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750353

RESUMO

BACKGROUND: To accurately predict the prognosis of glioma patients. METHODS: A total of 541 samples from the TCGA cohort, 181 observations from the CGGA database and 91 samples from our cohort were included in our study. Long non-coding RNAs (LncRNAs) associated with glioma WHO grade were evaluated by weighted gene co-expression network analysis (WGCNA). Five lncRNA features were selected out to construct prognostic signatures based on the Cox regression model. RESULTS: By weighted gene co-expression network analysis (WGCNA), 14 lncRNAs related to glioma grade were identified. Using univariate and multivariate Cox analysis, five lncRNAs (CYTOR, MIR155HG, LINC00641, AC120036.4 and PWAR6) were selected to develop the prognostic signature. The Kaplan-Meier curve depicted that the patients in high risk group had poor prognosis in all cohorts. The areas under the receiver operating characteristic curve of the signature in predicting the survival of glioma patients at 1, 3, and 5 years were 0.84, 0.92, 0.90 in the CGGA cohort; 0.8, 0.85 and 0.77 in the TCGA set and 0.72, 0.90 and 0.86 in our own cohort. Multivariate Cox analysis demonstrated that the five-lncRNA signature was an independent prognostic indicator in the three sets (CGGA set: HR = 2.002, p < 0.001; TCGA set: HR = 1.243, p = 0.007; Our cohort: HR = 4.457, p = 0.008, respectively). A nomogram including the lncRNAs signature and clinical covariates was constructed and demonstrated high predictive accuracy in predicting 1-, 3- and 5-year survival probability of glioma patients. CONCLUSION: We established a five-lncRNA signature as a potentially reliable tool for survival prediction of glioma patients.


Assuntos
Neoplasias Encefálicas/mortalidade , Biologia Computacional/métodos , Glioma/mortalidade , RNA Longo não Codificante/análise , Neoplasias Encefálicas/genética , Redes Reguladoras de Genes , Glioma/genética , Humanos , Nomogramas , Prognóstico , Modelos de Riscos Proporcionais
15.
Oxid Med Cell Longev ; 2021: 8873581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763177

RESUMO

Recent studies have recognized several risk factors for cardiopulmonary bypass- (CPB-) associated acute kidney injury (AKI). However, the lack of early biomarkers for AKI prevents practitioners from intervening in a timely manner. We reviewed the literature with the aim of improving our understanding of the risk factors for CPB-associated AKI, which may increase our ability to prevent or improve this condition. Some novel early biomarkers for AKI have been introduced. In particular, a combinational use of these biomarkers would be helpful to improve clinical outcomes. Furthermore, we discuss several interventions that are aimed at managing CPB-associated AKI, may increase the effect of renal replacement therapy (RRT), and may contribute to preventing CPB-associated AKI. Collectively, the conclusions of this paper are limited by the availability of clinical trial evidence and conflicting definitions of AKI. A guideline is urgently needed for CPB-associated AKI.


Assuntos
Injúria Renal Aguda/etiologia , Ponte Cardiopulmonar/efeitos adversos , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Humanos , Polimorfismo Genético , Terapia de Substituição Renal , Fatores de Risco
16.
Oncol Lett ; 21(4): 303, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33732379

RESUMO

Notch intracellular domain (NICD), also known as the activated form of Notch1 is closely associated with cell differentiation and tumor invasion. However, the role of NICD in glioblastoma (GBM) proliferation and the underlying regulatory mechanism remains unclear. The present study aimed to investigate the expression of NICD and Notch1 downstream gene HES5 in human GBM and normal brain samples and to further detect the effect of NICD on human GBM cell proliferation. For this purpose, western blotting and immunohistochemical staining were performed to analyze the expression of NICD in human GBM tissues, while western blotting and reverse-transcription quantitative PCR experiments were used to analyze the expression of Hes5 in human GBM tissues. A Flag-NICD vector was used to overexpress NICD in U87 cells and compound E and small interfering (si) Notch1 were used to downregulate NICD. Cellular proliferation curves were generated and BrdU assays performed to evaluate the proliferation of U87 cells. The results demonstrated that compared with normal brain tissues, the level of NICD protein in human GBM tissues was upregulated and the protein and mRNA levels of Hes5 were also upregulated in GBM tissues indicating that the Notch1 signaling pathway is activated in GBM. Overexpression of NICD promoted the proliferation of U87 cells in vitro while downregulation of NICD by treatment with compound E or siNotch1 suppressed the proliferation of U87 cells in vitro. In conclusion, NICD was upregulated in human GBM and NICD promoted GBM proliferation via the Notch1 signaling pathway. NICD may be a potential diagnostic marker and therapeutic target for GBM treatment.

18.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33558416

RESUMO

Photoperiod sensitivity is a key factor in plant adaptation and crop production. In the short-day plant soybean, adaptation to low latitude environments is provided by mutations at the J locus, which confer extended flowering phase and thereby improve yield. The identity of J as an ortholog of Arabidopsis ELF3, a component of the circadian evening complex (EC), implies that orthologs of other EC components may have similar roles. Here we show that the two soybean homeologs of LUX ARRYTHMO interact with J to form a soybean EC. Characterization of mutants reveals that these genes are highly redundant in function but together are critical for flowering under short day, where the lux1 lux2 double mutant shows extremely late flowering and a massively extended flowering phase. This phenotype exceeds that of any soybean flowering mutant reported to date, and is strongly reminiscent of the "Maryland Mammoth" tobacco mutant that featured in the seminal 1920 study of plant photoperiodism by Garner and Allard [W. W. Garner, H. A. Allard, J. Agric. Res. 18, 553-606 (1920)]. We further demonstrate that the J-LUX complex suppresses transcription of the key flowering repressor E1 and its two homologs via LUX binding sites in their promoters. These results indicate that the EC-E1 interaction has a central role in soybean photoperiod sensitivity, a phenomenon also first described by Garner and Allard. EC and E1 family genes may therefore constitute key targets for customized breeding of soybean varieties with precise flowering time adaptation, either by introgression of natural variation or generation of new mutants by gene editing.


Assuntos
Adaptação Fisiológica , Flores/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Fotoperíodo , Proteínas de Plantas/metabolismo , Soja/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/efeitos da radiação , Fenótipo , Melhoramento Vegetal , Proteínas de Plantas/genética , Soja/genética , Soja/crescimento & desenvolvimento , Soja/efeitos da radiação
19.
Oncol Rep ; 45(2): 595-605, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416158

RESUMO

Rho family GTPase 3 (RND3) is involved in multiple physiological activities involving the Rho kinase­dependent signaling pathway. The present study revealed a novel role of RND3 in the regulation of apoptosis in the brain. Using immunofluorescence and TUNEL assays, a decreased rate of brain apoptosis was observed in Rnd3­knockout mice. In addition, the function of RND3 in promoting apoptosis was determined in PC12 cells by immunoblotting assays and flow cytometry analysis in RNA interference and overexpression experiments. Furthermore, the present study demonstrated that Rnd3 and P65 protein interacted using immunoprecipitation analysis, and Rnd3 regulated apoptosis via its association with NF­κB P65. Notably, Rnd3 blocked the anti­apoptotic action of NF­κB P65 in vitro by downregulating P65. Therefore, RND3­NF­κB P65 represents a novel signaling pathway in the regulation of brain apoptosis. The present study suggested an alternative approach for the treatment of neurodegenerative diseases through regulation of apoptosis via the RND3­NF­κB P65 signaling pathway in the central nervous system.

20.
J Integr Plant Biol ; 63(6): 1004-1020, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33458938

RESUMO

Flowering time and stem growth habit determine inflorescence architecture in soybean, which in turn influences seed yield. Dt1, a homolog of Arabidopsis TERMINAL FLOWER 1 (TFL1), is a major controller of stem growth habit, but its underlying molecular mechanisms remain unclear. Here, we demonstrate that Dt1 affects node number and plant height, as well as flowering time, in soybean under long-day conditions. The bZIP transcription factor FDc1 physically interacts with Dt1, and the FDc1-Dt1 complex directly represses the expression of APETALA1 (AP1). We propose that FT5a inhibits Dt1 activity via a competitive interaction with FDc1 and directly upregulates AP1. Moreover, AP1 represses Dt1 expression by directly binding to the Dt1 promoter, suggesting that AP1 and Dt1 form a suppressive regulatory feedback loop to determine the fate of the shoot apical meristem. These findings provide novel insights into the roles of Dt1 and FT5a in controlling the stem growth habit and flowering time in soybean, which determine the adaptability and grain yield of this important crop.


Assuntos
Meristema/metabolismo , Meristema/fisiologia , Soja/metabolismo , Soja/fisiologia , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Flores/genética , Flores/metabolismo , Flores/fisiologia , Hábitos , Meristema/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Soja/genética
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