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1.
BMC Cancer ; 24(1): 451, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605343

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.


Assuntos
Carcinoma de Células Renais , Senescência Celular , Neoplasias Renais , Reprogramação Metabólica , Receptores de Prostaglandina E Subtipo EP4 , Humanos , Carcinoma de Células Renais/genética , Senescência Celular/genética , Análise de Sequência de RNA , Microambiente Tumoral/genética
2.
Nat Genet ; 56(3): 442-457, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361033

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Multiômica , Proteômica , Reprogramação Metabólica , Dicicloexilcarbodi-Imida , Progressão da Doença , Prognóstico
3.
J Transl Med ; 22(1): 55, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218866

RESUMO

Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.


Assuntos
Gencitabina , Neoplasias da Bexiga Urinária , Humanos , Reprogramação Metabólica , Sequência de Bases , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Análise de Sequência de RNA , Microambiente Tumoral , Ácido Graxo Sintase Tipo I/genética
4.
BMC Biol ; 21(1): 211, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37807042

RESUMO

BACKGROUND: Anthocyanin is a class of important secondary metabolites that determines colorful petals in chrysanthemum, a famous cut flower. 'Arctic Queen' is a white chrysanthemum cultivar that does not accumulate anthocyanin during the flowering stage. During the post-flowering stage, the petals of 'Arctic Queen' accumulate anthocyanin and turn red. However, the molecular mechanism underlying this flower color change remains unclear. RESULTS: In this study, by using transcriptome analysis, we identified CmNAC25 as a candidate gene promoting anthocyanin accumulation in the post-flowering stage of 'Arctic Queen'. CmNAC25 is directly bound to the promoter of CmMYB6, a core member of the MBW protein complex that promotes anthocyanin biosynthesis in chrysanthemum, to activate its expression. CmNAC25 also directly activates the promoter of CmDFR, which encodes the key enzyme in anthocyanin biosynthesis. CmNAC25 was highly expressed during the post-flowering stage, while the expression level of CmMYB#7, a known R3 MYB transcription factor interfering with the formation of the CmMYB6-CmbHLH2 complex, significantly decreased. Genetic transformation of both chrysanthemum and Nicotiana tabacum verified that CmNAC25 was a positive regulator of anthocyanin biosynthesis. Another two cultivars that turned red during the post-flowering stages also demonstrated a similar mechanism. CONCLUSIONS: Altogether, our data revealed that CmNAC25 positively regulates anthocyanin biosynthesis in chrysanthemum petals during the post-flowering stages by directly activating CmMYB6 and CmDFR. Our results thus revealed a crucial role of CmNAC25 in regulating flower color change during petal senescence and provided a target gene for molecular design breeding of flower color in chrysanthemum.


Assuntos
Antocianinas , Chrysanthemum , Antocianinas/análise , Antocianinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Chrysanthemum/genética , Chrysanthemum/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Flores/genética , Regulação da Expressão Gênica de Plantas
5.
Cancer Res ; 83(23): 3920-3939, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37729394

RESUMO

Fatty acid metabolism reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Increased lipid storage supports ccRCC progression, highlighting the importance of understanding the molecular mechanisms driving altered fatty acid synthesis in tumors. Here, we identified that malonyl-CoA decarboxylase (MLYCD), a key regulator of fatty acid anabolism, was downregulated in ccRCC, and low expression correlated with poor prognosis in patients. Restoring MLYCD expression in ccRCC cells decreased the content of malonyl CoA, which blocked de novo fatty acid synthesis and promoted fatty acid translocation into mitochondria for oxidation. Inhibition of lipid droplet accumulation induced by MLYCD-mediated fatty acid oxidation disrupted endoplasmic reticulum and mitochondrial homeostasis, increased reactive oxygen species levels, and induced ferroptosis. Moreover, overexpressing MLYCD reduced tumor growth and reversed resistance to sunitinib in vitro and in vivo. Mechanistically, HIF2α inhibited MLYCD translation by upregulating expression of eIF4G3 microexons. Together, this study demonstrates that fatty acid catabolism mediated by MLYCD disrupts lipid homeostasis to repress ccRCC progression. Activating MLYCD-mediated fatty acid metabolism could be a promising therapeutic strategy for treating ccRCC. SIGNIFICANCE: MLYCD deficiency facilitates fatty acid synthesis and lipid droplet accumulation to drive progression of renal cell carcinoma, indicating inducing MYLCD as a potential approach to reprogram fatty acid metabolism in kidney cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo
6.
Plant J ; 116(6): 1652-1666, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37696505

RESUMO

TEMPRANILLO1 (TEM1) is a transcription factor belonging to related to ABI3 and VP1 family, which is also known as ethylene response DNA-binding factor 1 and functions as a repressor of flowering in Arabidopsis. Here, a putative homolog of AtTEM1 was isolated and characterized from chrysanthemum, designated as CmTEM1. Exogenous application of ethephon leads to an upregulation in the expression of CmTEM1. Knockdown of CmTEM1 promotes floral initiation, while overexpression of CmTEM1 retards floral transition. Further phenotypic observations suggested that CmTEM1 involves in the ethylene-mediated inhibition of flowering. Transcriptomic analysis established that expression of the flowering integrator CmAFL1, a member of the APETALA1/FRUITFULL subfamily, was downregulated significantly in CmTEM1-overexpressing transgenic plants compared with wild-type plants but was verified to be upregulated in amiR-CmTEM1 lines by quantitative RT-PCR. In addition, CmTEM1 is capable of binding to the promoter of the CmAFL1 gene to inhibit its transcription. Moreover, the genetic evidence supported the notion that CmTEM1 partially inhibits floral transition by targeting CmAFL1. In conclusion, these findings demonstrate that CmTEM1 acts as a regulator of ethylene-mediated delayed flowering in chrysanthemum, partly through its interaction with CmAFL1.


Assuntos
Chrysanthemum , Proteínas de Plantas , Fatores de Transcrição , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Chrysanthemum/fisiologia , Etilenos/metabolismo , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Plantas/metabolismo
7.
Int J Biol Macromol ; 253(Pt 1): 126552, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37660849

RESUMO

Organophosphorus pesticides can inhibit the activity of acetylcholinesterase and cause neurological diseases. Therefore, it is crucial to establish an efficient and sensitive platform for organophosphorus pesticide detection. In this work, we extracted aloe polysaccharide (AP) from aloe vera with the number average molecular weight of 27760 Da and investigated its reducing property. We prepared aloe polysaccharide stabilized platinum nanoflowers (AP-Ptn NFs), their particle size ranges were 29.4-67.3 nm. Furthermore, AP-Ptn NFs exhibited excellent oxidase-like activity and the catalytic kinetics followed the typical Michaelis-Menten equation. They showed strong affinity for 3,3',5,5'-tetramethylbenzidine substrates. More importantly, we developed a simple and effective strategy for the sensitive colorimetric detection of organophosphorus pesticides in food using biocompatible AP-Ptn NFs. The detection range was 0.5 µg/L - 140 mg/L, which was wider than many previously reported nanozyme detection systems. This colorimetric biosensor had good selectivity and good promise for bioassay analysis.


Assuntos
Aloe , Técnicas Biossensoriais , Praguicidas , Praguicidas/análise , Compostos Organofosforados/análise , Acetilcolinesterase/química , Platina , Aloe/química , Colorimetria , Polissacarídeos/química
8.
Biomolecules ; 13(8)2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37627319

RESUMO

Many diseases in the human body are related to the level of L-cysteine. Therefore, it is crucial to establish an efficient, simple and sensitive platform for L-cysteine detection. In this work, we synthesized platinum palladium bimetallic nanoparticles (Van-Ptm/Pdn NPs) using vancomycin hydrochloride (Van) as a stabilizer, which exhibited high oxidase-like catalytic activity. In addition, the catalytic kinetics of the Van-Pt1/Pd1 NPs followed the typical Michaelis-Menten equation, exhibiting a strong affinity for 3,3',5,5'-tetramethylbenzidine substrates. More importantly, we developed a simple and effective strategy for the sensitive colorimetric detection of L-cysteine using biocompatible Van-Pt1/Pd1 NPs. The detection limit was low, at 0.07 µM, which was lower than the values for many previously reported enzyme-like detection systems. The colorimetric method of the L-cysteine assay had good selectivity. The established method for the detection of L-cysteine showed promise for biomedical analysis.


Assuntos
Colorimetria , Vancomicina , Humanos , Cisteína , Paládio , Platina
9.
Plant Sci ; 336: 111837, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37611834

RESUMO

Flavonoids, of which the major groups are flavones, flavonols, and anthocyanins, confer a variety of colors on plants. Bud sports with variation of floral colors occur occasionally during chrysanthemum cultivation. Although it has been reported that methylation at the promoter of CmMYB6 was related to anthocyanin contents, the regulatory networks of flavonoid biosynthesis still remain largely unknown in mutation of chrysanthemum. We compared phenotypes, pigment composition and transcriptomes in two chrysanthemum cultivars, 'Anastasia Dark Green' and 'Anastasia Pink', and regenerated bud sports of these cultivars with altered floral colors. Increased anthocyanins turned the 'Anastasia Dark Green' mutant red, while decreased anthocyanins turned the 'Anastasia Pink' mutant white. Moreover, total flavonoids were reduced in both mutants. Multiple flavonoid biosynthetic genes and regulatory genes encoding MYBs and bHLHs transcription factors were differentially expressed in pairwise comparisons of transcriptomes in 'Anastasia Dark Green' or 'Anastasia Pink' and their mutants at different flowering stages. Among these regulatory genes, the expression patterns of CmMYB6 and CmbHLH2 correlated to changes of anthocyanin contents, and down-regulation of CmMYB11 correlated to decreased total flavonoid contents in two mutants. CmMYB11 was shown to directly activate the promoter activities of CmCHS2, CmCHI, CmDFR, CmANS, CmFNS, and CmFLS. Furthermore, overexpression of CmMYB11 increased both flavonols and anthocyanins in tobacco petals. Our work provides new insights into regulatory networks involved in flavonoid biosynthesis and coloration in chrysanthemum.

10.
Heliyon ; 9(6): e16997, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37332935

RESUMO

Purpose: To systematically assess the clinical value of ultrasound radiomics in the prediction of microvascular invasion in hepatocellular carcinoma (HCC). Methods: Relevant articles were searched in PubMed, Web of Science, Cochrane Library, Embase and Medline and screened according to the eligibility criteria. The quality of the included articles was assessed based on the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. After article assessment and data extraction, the diagnostic performance of ultrasound radiomics was evaluated based on pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR), and the area under the curve (AUC) was calculated by generating the ROC curve. Meta-analysis was performed using Stata 15.1, and subgroup analysis was conducted to identify the sources of heterogeneity. A Fagan nomogram was generated to assess the clinical utility of ultrasound radiomics. Results: Five studies involving 1260 patients were included. Meta-analysis showed that ultrasound radiomics had a pooled sensitivity of 79% (95% CI: 75-83%), specificity of 70% (95% CI: 59-79%), PLR of 2.6 (95% CI: 1.9-3.7), NLR of 0.30 (95% CI: 0.23-0.39), DOR of 9 (95% CI: 5-16), and AUC of 0.81 (95% CI: 0.78-0.85). Sensitivity analysis indicated that the results were statistically reliable and stable, and no significant difference was identified during subgroup analysis. Conclusion: Ultrasound radiomics has favorable predictive performance in the microvascular invasion of HCC and may serve as an auxiliary tool for guiding clinical decision-making.

11.
Nat Commun ; 14(1): 2021, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37037808

RESUMO

Chrysanthemum (Chrysanthemum morifolium Ramat.) is a globally important ornamental plant with great economic, cultural, and symbolic value. However, research on chrysanthemum is challenging due to its complex genetic background. Here, we report a near-complete assembly and annotation for C. morifolium comprising 27 pseudochromosomes (8.15 Gb; scaffold N50 of 303.69 Mb). Comparative and evolutionary analyses reveal a whole-genome triplication (WGT) event shared by Chrysanthemum species approximately 6 million years ago (Mya) and the possible lineage-specific polyploidization of C. morifolium approximately 3 Mya. Multilevel evidence suggests that C. morifolium is likely a segmental allopolyploid. Furthermore, a combination of genomics and transcriptomics approaches demonstrate the C. morifolium genome can be used to identify genes underlying key ornamental traits. Phylogenetic analysis of CmCCD4a traces the flower colour breeding history of cultivated chrysanthemum. Genomic resources generated from this study could help to accelerate chrysanthemum genetic improvement.


Assuntos
Chrysanthemum , Chrysanthemum/genética , Filogenia , Melhoramento Vegetal , Perfilação da Expressão Gênica , Flores/genética , Cromossomos
12.
Medicine (Baltimore) ; 101(40): e29999, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36221346

RESUMO

BACKGROUND: To compare the effects of thermal softening of double-lumen endotracheal tubes (DLT) at different temperatures during fiberoptic bronchoscopy (FOB)-guided intubation. METHODS: We randomly divided 144 patients undergoing thoracic surgery into 4 groups as follows: T1 (T = 24 ± 1°C, n = 36), T2 (T = 36 ± 1°C, n = 36), T3 (T = 40 ± 1°C, n = 36), and T4 (T = 48 ± 1°C, n = 36). All groups underwent FOB-guided double-lumen endotracheal intubation and positioning. We recorded the duration of positioning and intubation using DLT, intubation resistance (IR), the success rate of the first attempt at endotracheal intubation, and the incidence of postoperative vocal cord injury and hoarseness. RESULTS: The time to intubation was longer in the T1 group than that in the T2, T3, and T4 groups (P < .05). The time for positioning was longer in the T4 group than that in the T1, T2, and T3 groups (P < .05). IR was lower in the T3 and T4 groups than those in T1 and T2 groups (P < .05). The success rate of the first attempt at endotracheal intubation was higher in the T2, T3, and T4 groups than that in the T1 group (P < .05). Postoperative glottic injury and hoarseness were higher in the T1 and T2 groups than those in the T3 and T4 groups (P < .05). CONCLUSION: A thermally softened DLT shortened the time to intubation, reduced the IR, improved the success rate of the first attempt at endotracheal intubation, and lowered the incidence of postoperative glottic injury and hoarseness. The optimal tube temperature for FOB-guided intubation of thermally softened DLT was 40 ± 1°C.


Assuntos
Broncoscopia , Intubação Intratraqueal , Broncoscópios , Broncoscopia/efeitos adversos , Broncoscopia/instrumentação , Rouquidão/epidemiologia , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Temperatura
13.
Cancer Lett ; 550: 215918, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150633

RESUMO

Although obesity contributes to tumor incidence and progression in various cancers, whether obesity impacts the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) remains largely under-explored. We generated NSCLC xenograft model in diet-induced obese mice and identified that TFEB is critical to accelerate obesity-related NSCLC progression with mimic intrinsic functions on tumor biology. Mechanically, TFEB binds directly to Siglec-15 promoter to upregulate Siglec-15 expression and binds to Hk2 and Ldha promoters to enhance glycolytic flux in NSCLC cells, which restrain the expansion and cytotoxic function of CD8+ T cells while maintain suppressive Treg cells in TME, jointly promoting immune evasion of NSCLC cells in obesity. Blocking tumor TFEB improves the therapeutic efficiency of anti-PD-1 in obese mice. Altogether, our data identify essential roles of TFEB in remodeling immunosuppressive TME and promoting NSCLC development in obesity, providing scientific rational for TFEB as a potential biomarker to predict immune checkpoint blockade efficiency in obese NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Evasão da Resposta Imune , Imunoglobulinas , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana , Camundongos , Camundongos Obesos , Obesidade/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/uso terapêutico , Microambiente Tumoral , Regulação para Cima
14.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 427-438, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818225

RESUMO

In the recent century, Kidney cancer has emerged as one of the critical renal diseases. Therefore, we analyzed gene expression profiles of non-metastatic kidney cancer to find mechanisms associated with the early-stage pathogenesis of the disease. We concentrated on the most dysregulated genes in expression to discover possible unknown proliferative molecular mechanisms and oncogenic pathways promoting kidney renal cancer growth. Survival analysis, expression profiling, and gene set over-representation analysis were conducted on the most upregulated and most down-regulated genes alongside the hub genes. Our results demonstrated that pathways engaged in the metabolism of amino acids and carbohydrates and those involved in peroxisome organization were shown to be important in developing benign tumors. Furthermore, upregulation of genes such as CXCL9 and 10 genes and CXCR4 in chemokine response pathways would bolster differentiation and engagement of immune cells in the tumor microenvironment. C3, one of the essential members of the complement system, with a high degree and betweenness centrality in the PPI network, upregulated significantly not only in our analysis but also in the validation expression profiling results and survival analysis. We also identified genes such as TYROBP, ITGB2, and EGFR to be engaged in both immunological pathways and superoxide pathways. Furthermore, we found that downregulation of Aldolase B engaged in Glycolysis and Gluconeogenesis pathways would help develop benign tumors. Finally, many top hub genes, including TYMS, PTPRC, AURKA, FN1, UBE2C, and CD53 were proposed to be engaged in the progression of non-metastatic renal tumors. This holistic interrogation calls attention to investigate further and experimentally validate the proposed molecular mechanisms.


Assuntos
Redes Reguladoras de Genes , Neoplasias Renais , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Mapas de Interação de Proteínas/genética , Microambiente Tumoral
15.
Dis Markers ; 2022: 7925097, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465266

RESUMO

We previously confirmed that transducer of ERBB2, 1 (TOB1) gene, can induce autophagy in gastric cancer cells. Studies have shown the biogenesis of exosomes overlaps with different autophagy processes, which helps to maintain the self-renewal and homeostasis of body cells. This study is aimed at verifying whether overexpressing TOB1 induces autophagy by secreting exosomes in gastric cancer cells and its underlying mechanisms. Differential ultracentrifugation was used to extracted the exosomes from the culture medium of gastric cancer cell line AGS-TOB1 ectopically overexpressing TOB1 (exo-AGS-TOB1, experimental group) and AGS-empty-vector cell line with low expression of endogenous TOB1 (exo-AGS-Vector, control group). Exosomal markers CD9 and TSG101 were determined in both the cell supernatants of exo-AGS-TOB1 and exo-AGS-Vector by Western blot. Under the transmission electron microscope (TEM), the exosomes were round and saucer-like vesicles with double-layer membrane structure, and the vesicles showed different translucency due to different contents. The peak size of exosomes detected by nanoparticle tracking analysis (NTA) was about 100 nm. When the exosomes of exo-AGS-TOB1 and exo-AGS-Vector were cocultured with TOB1 knockdown gastric cancer cell line HGC-27-TOB1-6E12 for 48 hours, the conversion of autophagy-related protein LC3-I to LC3-II in HGC-27-TOB1-6E12 gastric cancer cells cocultured with exo-AGS-TOB1 was significantly higher than that in the control group, and the ratio of LC3-II/LC3-I was statistically different (P < 0.05). More autophagosomes in HGC-27-TOB1-6E12 cells cocultured with exo-AGS-TOB1 for 48 hours were observed under TEM, while fewer autophagosomes were found in the control group. Lastly, miRNAs were differentially expressed by cell supernatant-exosomal whole transcriptome sequencing. Thus, our results provide new insights into TOB1-induced autophagy in gastric cancer.


Assuntos
Exossomos , MicroRNAs , Neoplasias Gástricas , Autofagia , Exossomos/genética , Exossomos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Transdutores , Proteínas Supressoras de Tumor/genética
16.
Front Immunol ; 13: 837991, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359973

RESUMO

Background: Prostate cancer (PCa) is the most common malignant tumor in men. Although clinical treatments of PCa have made great progress in recent decades, once tolerance to treatments occurs, the disease progresses rapidly after recurrence. PCa exhibits a unique metabolic rewriting that changes from initial neoplasia to advanced neoplasia. However, systematic and comprehensive studies on the relationship of changes in the metabolic landscape of PCa with tumor recurrence and treatment response are lacking. We aimed to construct a metabolism-related gene landscape that predicts PCa recurrence and treatment response. Methods: In the present study, we used differentially expressed gene analysis, protein-protein interaction (PPI) networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression to construct and verify a metabolism-related risk model (MRM) to predict the disease-free survival (DFS) and response to treatment for PCa patients. Results: The MRM predicted patient survival more accurately than the current clinical prognostic indicators. By using two independent PCa datasets (International Cancer Genome Consortium (ICGC) PCa and Taylor) and actual patients to test the model, we also confirmed that the metabolism-related risk score (MRS) was strongly related to PCa progression. Notably, patients in different MRS subgroups had significant differences in metabolic activity, mutant landscape, immune microenvironment, and drug sensitivity. Patients in the high-MRS group were more sensitive to immunotherapy and endocrine therapy, while patients in the low-MRS group were more sensitive to chemotherapy. Conclusions: We developed an MRM, which might act as a clinical feature to more accurately assess prognosis and guide the selection of appropriate treatment for PCa patients. It is promising for further application in clinical practice.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Microambiente Tumoral
17.
Front Oncol ; 12: 809589, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299748

RESUMO

The strong invasive and metastatic abilities of oral squamous cell carcinoma (OSCC) cells in the early stage are the main reason for its poor prognosis. The early diagnosis and treatment of OSCC may reduce the metastasis rate and improve the survival rate. The aim of this study was to explore candidate biomarkers related to the prognosis and progression of OSCC. We performed weighted gene coexpression network analysis to identify key modules and genes associated with OSCC and intersected the differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA)-OSCC and GSE30784 datasets. Next, we performed survival analysis and immunohistochemistry to screen and validate the hub gene insulin-like growth factor 2 (IGF2) mRNA binding protein 2 IGF2BP2. We also used TCGA pan-cancer data to verify that IGF2BP2 was expressed at high levels in a variety of cancers and was related to a poor prognosis in patients. Furthermore, we divided patients with OSCC into high and low expression groups based on the median expression level of IGF2BP2. Gene set enrichment analysis (GSEA) showed that IGF2BP2 led to a poor prognosis in OSCC by affecting cancer-related (epithelial-mesenchymal transition, glycolysis, cell cycle, etc.) and immune-related biological functions and pathways. Single-sample GSEA (ssGSEA), CIBERSORT, and xCell algorithms helped reveal that high IGF2BP2 expression was accompanied by a significant reduction in the immune score, stromal score, and microenvironment score and a decrease in the number of infiltrating CD8+ T cells in OSCC. In addition, silencing IGF2BP2 suppressed the proliferation, migration, and invasion of OSCC cells. In general, IGF2BP2 is a potential biomarker for the progression, immunotherapy response, and prognosis of OSCC.

18.
Plant Mol Biol ; 108(1-2): 51-63, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34714494

RESUMO

KEY MESSAGE: An R2R3-MYB transcription factor, CmMYB9a, activates floral coloration in chrysanthemum by positively regulating CmCHS, CmDFR and CmFNS, but inhibiting the expression of CmFLS. Chrysanthemum is one of the most popular ornamental plants worldwide. Flavonoids, such as anthocyanins, flavones, and flavonols, are important secondary metabolites for coloration and are involved in many biological processes in plants, like petunia, snapdragon, Gerbera hybrida, as well as chrysanthemum. However, the metabolic regulation of flavonoids contributing to chrysanthemum floral coloration remains largely unexplored. Here, an R2R3-MYB transcription factor, CmMYB9a, was found to be involved in flavonoid biosynthesis. Phylogenetic analysis and amino acid sequence analysis suggested that CmMYB9a belonged to subgroup 7. Transient overexpression of CmMYB9a in flowers of chrysanthemum cultivar 'Anastasia Pink' upregulated the anthocyanin-related and flavone-related genes and downregulated CmFLS, which led to the accumulation of anthocyanins and flavones. We further demonstrated that CmMYB9a independently activates the expression of CmCHS, CmDFR and CmFNS, but inhibits the expression of CmFLS. Overexpression of CmMYB9a in tobacco resulted in increased anthocyanins and decreased flavonols in the petals by upregulating NtDFR and downregulating NtFLS. These results suggest that CmMYB9a facilitates metabolic flux into anthocyanin and flavone biosynthesis. Taken together, this study functionally characterizes the role of CmMYB9a in regulating the branched pathways of flavonoids in chrysanthemum flowers.


Assuntos
Antocianinas/biossíntese , Chrysanthemum/metabolismo , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Chrysanthemum/genética , Cor , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase , Nicotiana , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-Híbrido
19.
IET Nanobiotechnol ; 15(1): 135-146, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34694728

RESUMO

Nowadays, the problem of oil spill and organic solvent pollution has become more and more serious, and developing a green and efficient treatment method has become a research hotspot. Herein, the preparation of porous super-hydrophobic aerogel by directional freezing with cellulose nanofibre (CNF) as the base material, polyvinyl alcohol (PVA) as the cross-linking agent and montmorillonite (MMT) as the modifier and filler, followed by hydrophobic treatment with chemical vapour deposition is reported. The prepared composite aerogel presented three-dimensional inter-perforation network structure, low density (26.52 mg⋅cm-3 ), high porosity (96.1 %) and good hydrophobicity (water contact angle of 140°). Notably, the composite aerogel has a good adsorption effect on different oils and organic solutions, and its adsorption capacity can reach 40-68 times of its initial weight. After complete adsorption, the aerogel could be easily collected. More importantly, the composite aerogel had high strength, whose compressive stress at 70 % strain reached 0.15 MPa and could bear over 1290 times its weight without deformation after 2 weeks. A new, green, simple and efficient absorbent for the adsorption of oils and organic solvents is provided.


Assuntos
Nanofibras , Bentonita , Celulose , Géis , Interações Hidrofóbicas e Hidrofílicas , Óleos de Plantas , Álcool de Polivinil
20.
Plant Physiol Biochem ; 166: 1109-1120, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328869

RESUMO

Flavonoids confer a wide color range to plants, thus influencing the flower quality and commercial value of various ornamental plants. Flavones and flavonols are colorless pigments that are distinct from the colored anthocyanins. Flavones and flavonols are transformed from flavanones and dihydrokaempferol, which are catalyzed by flavone synthase (FNS) and flavonol synthase (FLS), respectively, and play important roles in regulating plant growth and development, and resistance to various stresses, in addition to coloration. However, few studies have been conducted on CmFNS and CmFLS genes in chrysanthemums. In this study, we isolated and identified CmFNS and CmFLS from Chrysanthemum morifolium. CmFNS and CmFLS were constitutively expressed at different levels in various C. morifolium organs, and in vitro catalytic activity of CmFNS and CmFLS was verified. CmFNS- and CmFLS-overexpressing tobacco plants exhibited phenotypes that accumulated more flavones and flavonols, respectively, but less anthocyanins. Moreover, the transcripts of CmFNS were negatively correlated with flower color, whereas CmFLS presented an opposite trend compared to CmFNS in five flower color cultivars with different anthocyanin levels. These findings suggest that CmFNS and CmFLS act as important regulators of flavone and flavonol biosynthesis, respectively, and dicate flower coloration in chrysanthemums.


Assuntos
Chrysanthemum , Flavonas , Antocianinas , Chrysanthemum/genética , Cor , Flores/genética , Regulação da Expressão Gênica de Plantas , Oxirredutases , Proteínas de Plantas
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