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1.
Front Cell Neurosci ; 17: 1201295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538851

RESUMO

Social isolation (SI) exerts diverse adverse effects on brain structure and function in humans. To gain an insight into the mechanisms underlying these effects, we conducted a systematic analysis of multiple brain regions from socially isolated and group-housed dogs, whose brain and behavior are similar to humans. Our transcriptomic analysis revealed reduced expression of myelin-related genes specifically in the white matter of prefrontal cortex (PFC) after SI during the juvenile stage. Despite these gene expression changes, myelin fiber organization in PFC remained unchanged. Surprisingly, we observed more mature oligodendrocytes and thicker myelin bundles in the somatosensory parietal cortex in socially isolated dogs, which may be linked to an increased expression of ADORA2A, a gene known to promote oligodendrocyte maturation. Additionally, we found a reduced expression of blood-brain barrier (BBB) structural components Aquaporin-4, Occludin, and Claudin1 in both PFC and parietal cortices, indicating BBB disruption after SI. In agreement with BBB disruption, myelin-related sphingolipids were increased in cerebrospinal fluid in the socially isolated group. These unexpected findings show that SI induces distinct alterations in oligodendrocyte development and shared disruption in BBB integrity in different cortices, demonstrating the value of dogs as a complementary animal model to uncover molecular mechanisms underlying SI-induced brain dysfunction.

2.
Materials (Basel) ; 15(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35806542

RESUMO

Laser surface texture is very effective in antifriction systems, but its applications and research in dry friction are not enough. In this study, the groove texture was prepared on the surface of 0Cr17Ni7Al stainless steel, a common material of sliding bearing, by nanosecond and femtosecond laser, respectively. The tribological properties of the two kinds of laser groove textures with different collision frequencies were studied in depth. The results show that the friction coefficients of groove texture prepared by nanosecond and picosecond lasers are lower than that of the untextured surface. The antifriction characteristics of the laser texture are very good. The average friction coefficient of nanosecond texture at the rotation radius of 15 mm is Z = 0.7318. The best friction-reducing effect is achieved. In general, the friction coefficient of nanosecond texture is lower than that of picosecond texture. When the friction radius is 22.5 mm and the number of collisions is 24,000, the lowest picosecond texture wear rate is H = 3.342 × 10-4 mm3/N·mm. However, when the radius is 15 mm and the collision frequency is 36,000 times, the wear rate of nanosecond texture reaches the highest H = 13.680 × 10-4 mm3/N·mm. The wear rate of the untextured surface has been exceeded. It can be seen that not all rotation radius textures are more wear-resistant than untextured surfaces. In addition, nanosecond groove texture and picosecond groove texture seem to produce different tribological properties. It is found that, under the same friction experimental conditions, different collision frequencies will affect the friction and wear properties of nanosecond and picosecond groove-textured surfaces.

3.
Front Cell Dev Biol ; 10: 810687, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223840

RESUMO

Cancer stem cells (CSCs) usually account for a very small tumor cell population but play pivotal roles in human cancer development and recurrence. A fundamental question in cancer biology is what genetic and epigenetic changes occur in CSCs. Here we show that the in-situ global levels of DNA cytosine modifications, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), are similar between liver cancer stem-like (LCSL) cells and paratumor liver cells of liver cancer patients. We then developed a robust method combining immunohistochemistry, laser capture microdissection and genome sequencing with ultra-low-input cells (CIL-seq) to study the detailed genetic and DNA methylation changes in human LCSL cells. We first used clinical samples of mixed hepatocellular carcinoma-cholangiocarcinoma (HCC-CCA) with stem cell features to investigate human LCSL cells. The CIL-seq analysis of HCC-CCA and HCC patients showed that LCSL cells had strong spatial genetic and epigenetic heterogeneity. More interestingly, although the LCSL cells had some potential key changes in their genome, they had substantially fewer somatic single nucleotide variants (SNVs), copy number alterations (CNAs) and differentially methylated regions than other tumor parenchymal cells. The cluster analysis of SNVs, CNAs, DNA methylation patterns and spatial transcriptomes all clearly showed that the LCSL cells were clustered with the paratumor liver cells. Thus, spatial multiomics analysis showed that LCSL cells had only minor genetic and epigenetic changes compared with other tumor parenchymal cells. Targeting key changes in CSCs, not just changes in bulk tumor cells, should be more effective for human cancer therapy.

4.
Nanomaterials (Basel) ; 13(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36616062

RESUMO

As a kind of sliding bearing, the gas bearing is widely used in high-speed rotating machinery. It realizes energy cleaning in the field of high-speed rotating machinery. In order to solve the problem of reducing the service life of gas bearings due to friction during startup and shutdown, we use micromachining technology to process groove textures with different groove widths on the surface of 0Cr17Ni7Al, a common material for gas bearings. A ball-disc friction contrast test is conducted under dry friction conditions with and without texture. The experiment shows that the lowest average friction coefficient of 0.8 mm texture is σ = 0.745. When the friction radius is 22.5 mm, the wear rate of 1.0 mm texture is the lowest at ω = 3.118 × 10-4mm3/N·mm. However, the maximum friction coefficient reached is σ = 0.898. Under the nanometer scale, the contact between friction pairs is fully analyzed. The influence mechanism of different groove widths, friction impacts and climbing heights on the friction and wear properties of the micromechanical groove texture on the surface of 0Cr17Ni7Al stainless steel is studied at the nano-fractal scale. The effects of different width grooves on the surface texture and tribological properties of the micromachine are studied.

5.
Aging (Albany NY) ; 12(23): 23849-23871, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33221766

RESUMO

Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Biologia Computacional , Genômica , Neoplasias Hepáticas/genética , Integração de Sistemas , Proteínas 14-3-3/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Proliferação de Células , Variações do Número de Cópias de DNA , Metilação de DNA , Bases de Dados Genéticas , Fatores de Transcrição E2F/genética , Epigênese Genética , Exorribonucleases/genética , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Mutação , Gradação de Tumores , Osteopontina/genética , Fenótipo , Proteína Supressora de Tumor p53/genética
6.
Mol Genet Genomic Med ; 8(4): e1112, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32061057

RESUMO

BACKGROUND: Long noncoding RNA (LncRNA) XIST is one of the genes that exists in different types of cancers. Earlier researches showed that XIST can advance the progression of colorectal cancer. Nevertheless, the potential molecular mechanism of XIST in combination with miR-93-5p has not been explored in colorectal cancer. METHODS: We performed qRT-PCR to explore the level of XIST. And a serious experiments in vitro and in vivo were performed to explore the function of XIST. The relationship between XIST/HIF-1A and miR-93-5p was confirmed by RIP and dual-luciferase assays. RESULTS: In the present research, our team demonstrated the upregulation of XIST expression, which was related to tumor progression, and the downregulation of miR-93-5p in cells and tissues of colorectal cancer. XIST is the competitive endogenous RNA of miR-93-5p to promote HIF-1A, and then the upregulated AXL level facilitates the EMT process, migration, and proliferation of colorectal cancer. At last, we proved that XIST enhanced the in vivo and in vitro activities of colorectal cancer by regulating AXL signaling. CONCLUSION: In summary, the above results indicate that XIST promotes colorectal cancer tumorigenesis by regulating miR-93-5p/HIF-1A/AXL signaling pathway, which will supply a novel perspective to diagnose and treat colorectal cancer disease.


Assuntos
Neoplasias Colorretais/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Longo não Codificante/genética , Receptores Proteína Tirosina Quinases/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/genética , RNA Longo não Codificante/metabolismo , Receptores Proteína Tirosina Quinases/genética , Transdução de Sinais , Regulação para Cima , Receptor Tirosina Quinase Axl
7.
Natl Sci Rev ; 7(3): 671-685, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34692086

RESUMO

Central precocious puberty (CPP) refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone (GnRH). Previously, loss-of-function mutations in human MKRN3, encoding a putative E3 ubiquitin ligase, were found to contribute to about 30% of cases of familial CPP. MKRN3 was thereby suggested to serve as a 'brake' of mammalian puberty onset, but the underlying mechanisms remain as yet unknown. Here, we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic GnRH1. MKRN3 interacts with and ubiquitinates MBD3, which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2. Our findings have thus delineated a molecular mechanism through which the MKRN3-MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.

8.
Cell Stem Cell ; 25(1): 54-68.e5, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31271748

RESUMO

Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. The intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed. Here we show that Arid1a, a key component of the SWI/SNF chromatin remodeling complex, controls liver regeneration and gene expression associated with emergence of injury-induced liver-progenitor-like cells (LPLCs). Hepatocyte-specific Arid1a ablation reduces LPLC gene expression in several models of periportal liver injury and impairs liver regeneration, leading to organ dysfunction. Arid1a establishes a permissive chromatin state at LPLC-enriched genes during homeostasis, suggesting it endows hepatocytes with competence to respond to injury-induced signals. Consistently, Arid1a facilitates binding of YAP, a critical regeneration signaling pathway, to LPLC-enriched genes, and Arid1a deletion prevents their YAP-associated induction following injury. Together, these findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Hepatócitos/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Autorrenovação Celular , Montagem e Desmontagem da Cromatina , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Homeostase , Regeneração Hepática , Camundongos , Camundongos Transgênicos , Transdução de Sinais , Proteínas de Sinalização YAP
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(1): 49-58, 2019 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-30703794

RESUMO

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS: The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.


Assuntos
Apendicite/diagnóstico , Apendicite/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Apendicectomia , China , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Onco Targets Ther ; 11: 7795-7803, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464527

RESUMO

BACKGROUND: Protein tyrosine phosphatase, receptor type F (PTPRF) is an important phosphatase playing roles in regulating cell growth, differentiation and oncogenic transformation. Overexpression of PTPRF has been observed in non-small cell lung cancer, but its clinical significance in other malignancies is still unknown. METHODS: We explored the expression pattern of PTPRF in gastric adenocarcinoma by using RT-qPCR and immunohistochemistry staining. The clinical significance of PTPRF was evaluated by univariate and multivariate analyses. Furthermore, the signaling pathways downstream of PTPRF was investigated by knockdown and overexpression assays combined with cellular studies. RESULTS: We found a remarkable down-regulation of PTPRF in gastric adenocarcinomas, which was significantly associated with advanced tumor TNM stages. Survival analysis showed that lower PTPRF level indicated a poorer overall survival of gastric adenocarcinoma patients. By conducting knockdown and overexpression studies in gastric adenocarcinoma cells, we revealed the role of PTPRF on inhibiting extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation and its downstream signaling. Consistent with clinical findings, cellular results demonstrated that overexpressing PTPRF can significantly inhibit tumor migration and invasion, while silencing PTPRF showed opposite effects. CONCLUSION: In conclusion, patients with lower PTPRF expression in gastric adenocarcinoma tissues were more predisposed to advanced tumor stage and unfavorable prognosis.

11.
Genome Med ; 10(1): 42, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29848370

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the one of the most common cancers and lethal diseases in the world. DNA methylation alteration is frequently observed in HCC and may play important roles in carcinogenesis and diagnosis. METHODS: Using the TCGA HCC dataset, we classified HCC patients into different methylation subtypes, identified differentially methylated and expressed genes, and analyzed cis- and trans-regulation of DNA methylation and gene expression. To find potential diagnostic biomarkers for HCC, we screened HCC-specific CpGs by comparing the methylation profiles of 375 samples from HCC patients, 50 normal liver samples, 184 normal blood samples, and 3780 samples from patients with other cancers. A logistic regression model was constructed to distinguish HCC patients from normal controls. Model performance was evaluated using three independent datasets (including 327 HCC samples and 122 normal samples) and ten newly collected biopsies. RESULTS: We identified a group of patients with a CpG island methylator phenotype (CIMP) and found that the overall survival of CIMP patients was poorer than that of non-CIMP patients. Our analyses showed that the cis-regulation of DNA methylation and gene expression was dominated by the negative correlation, while the trans-regulation was more complex. More importantly, we identified six HCC-specific hypermethylated sites as potential diagnostic biomarkers. The combination of six sites achieved ~ 92% sensitivity in predicting HCC, ~ 98% specificity in excluding normal livers, and ~ 98% specificity in excluding other cancers. Compared with previously published methylation markers, our markers are the only ones that can distinguish HCC from other cancers. CONCLUSIONS: Overall, our study systematically describes the DNA methylation characteristics of HCC and provides promising biomarkers for the diagnosis of HCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Ilhas de CpG/genética , Bases de Dados Genéticas , Genes Neoplásicos/genética , Humanos
12.
Sci Rep ; 8(1): 3339, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463849

RESUMO

Although numerous studies on kidney renal clear cell carcinoma (KIRC) were carried out, the dynamic process of tumor formation was not clear yet. Inadequate attention was paid on the evolutionary paths among somatic mutations and their clinical implications. As the tumor initiation and evolution of KIRC were primarily associated with SNVs, we reconstructed an evolutionary process of KIRC using cross-sectional SNVs in different pathological stages. KIRC driver genes appeared early in the evolutionary tree, and the genes with moderate mutation frequency showed a pattern of stage-by-stage expansion. Although the individual gene mutations were not necessarily associated with survival outcome, the evolutionary paths such as VHL-PBRM1 and FMN2-PCLO could indicate stage-specific prognosis. Our results suggested that, besides mutation frequency, the evolutionary relationship among the mutated genes could facilitate to identify novel drivers and biomarkers for clinical utility.


Assuntos
Carcinogênese , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Mutação , Estudos Transversais , Progressão da Doença , Evolução Molecular , Humanos , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Análise de Sobrevida
13.
Biochim Biophys Acta Mol Basis Dis ; 1864(6 Pt B): 2266-2273, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29317334

RESUMO

Long noncoding RNAs (lncRNAs) have been gradually emerging as important regulators in various biological processes and diseases, while the contributions of lncRNAs to atherosclerosis remain largely unknown. Our previous work has discovered atherosclerosis associated protein-coding genes by transcriptome sequencing of rabbit models. Here we investigated the roles of lncRNAs in atherosclerosis. We defined a stringent set of 3736 multi-exonic lncRNA transcripts in rabbits. All lncRNAs are firstly reported and 609 (16.3%) of them are conserved in 13 species. Rabbit lncRNAs have similar characteristics to lncRNAs in other mammals, such as relatively short length, low expression, and highly tissue-specificity. The integrative analysis of lncRNAs and co-expressed genes characterize diverse functions of lncRNAs. Comparing two kinds of atherosclerosis models (LDLR-deficient WHHL rabbits and cholesterol-fed NZW rabbits) with their corresponding controls, we found the expression changes of two rabbit models were similar in aorta in but different in liver. The shared change in aorta revealed a subset of lncRNAs involved in immune response, while the cholesterol-fed NZW rabbits showed broader lncRNA expression changes in skeletal muscle system compared to WHHL rabbits. These atherosclerosis-associated lncRNAs and genes provide hits for the experimental validation of lncRNA functions. In summary, our study systematically identified rabbit lncRNAs for the first time and provides new insights for understanding the functions of lncRNAs in atherosclerosis. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.


Assuntos
Aorta/metabolismo , Aterosclerose/metabolismo , Regulação da Expressão Gênica , Fígado/metabolismo , RNA Longo não Codificante/biossíntese , Animais , Aorta/patologia , Aterosclerose/patologia , Modelos Animais de Doenças , Fígado/patologia , Coelhos
14.
Biomed Res Int ; 2017: 1204082, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28393072

RESUMO

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Colágeno Tipo XI/biossíntese , Neoplasias Esofágicas/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Povo Asiático/genética , População Negra/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Colágeno Tipo XI/genética , Metilação de DNA/genética , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , População Branca/genética
15.
Comb Chem High Throughput Screen ; 20(2): 174-181, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28124598

RESUMO

AIM AND OBJECTIVE: Gastric cancer is one of the most common cancers and has very high incidence and mortality rate in Asian population. To tackle the problems of infiltration and heterogeneity, more accurate biomarkers for diagnosis and prognosis as well as effective targets for treatment are needed to achieve better outcomes of gastric cancer patients. Recently, methods and algorithms for analyzing high-throughput sequencing data have greatly facilitated the molecular profiling of gastric cancer. Nevertheless, prognostic biomarkers for gastric cancer that can be potentially applied in clinic are still lacking. MATERIALS AND METHODS: In this study, we performed differential regulatory analysis based on gene co-expression network for four different cohorts of Asian gastric cancer samples and their clinical data. RESULTS: We identified a 36-gene prognostic signature specific for gastric cancer, particularly for Asian population. We further analyzed differential regulatory patterns related to these featured genes, such as C1S, and suggested hypotheses for investigating their roles in gastric cancer pathogenesis. CONCLUSION: Findings from present study suggest a 36-gene signature which is based on differential regulatory analysis and can predict the prognosis of gastric cancer. Our research explores molecular mechanism of gastric cancer at transcriptional regulation level and provides potential drug targets. This integrated biomarker searching scheme is extendable to other cancer study for not only prognostic prediction, but also pathogenesis.


Assuntos
Perfilação da Expressão Gênica , Neoplasias Gástricas/diagnóstico , Povo Asiático , Biomarcadores Tumorais/análise , Estudos de Coortes , Redes Reguladoras de Genes , Humanos , Prognóstico , Neoplasias Gástricas/genética
16.
Oncotarget ; 7(52): 86051-86063, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27852072

RESUMO

In this study, we aimed to elucidate the clinical significance and underlying mechanisms of BRG1 in colon cancer. In the clinical analysis, overexpression of BRG1 correlates with colon cancer progression in two cohorts (n = 191 and n = 75). Kaplan-Meier survival analysis revealed that BRG1 is a prognosis predictor for overall survival (P < 0.001) and disease-free survival (P = 0.001). Knocking down BRG1 expression significantly suppressed the proliferation and invasion in colon cancer cells. The expression pattern of WNT3A is consistent with BRG1 in colon cancer tissues and WNT3A expression was inhibited in BRG1 knockdown cells. In addition, restoring WNT3A expression rescues the inhibition of cell proliferation and invasion induced by BRG1. In this study, we demonstrate that BRG1 may contribute to colon cancer progression through upregulating WNT3A expression.


Assuntos
Neoplasias do Colo/etiologia , DNA Helicases/fisiologia , Proteínas Nucleares/fisiologia , Fatores de Transcrição/fisiologia , Proteína Wnt3A/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico
17.
Tohoku J Exp Med ; 236(4): 311-8, 2015 08.
Artigo em Inglês | MEDLINE | ID: mdl-26268776

RESUMO

Fibroblast growth factor receptor 2 (FGFR2) has been proved to be a significant prognostic factor and a potential therapeutic target in several types of cancer, including gastric cancer. FGFR2 consists two isoforms: FGFR2-IIIb and FGFR2-IIIc, which can be stimulated by different ligands and trigger different downstream signaling pathways. As a specific ligand to FGFR2-IIIb, fibroblast growth factor 10 (FGF10) is expressed in the gastric mesenchyme cell and is involved in stomach development and morphogenesis, but its expression and clinical significance is not well elucidated in gastric cancer. We analyzed FGF10 expression by immunohistochemistry in 178 samples of gastric adenocarcinoma (134 male and 44 female patients, with the average age of 63.2 years old and the average follow-up of 21.6 months). Using the arbitrarily scoring method based on positive cell percentage and staining intensity, we sub-divided the patients into FGF10 high-expression group (58 patients) and low-expression group (120 patients). We thus found that FGF10 expression is significantly associated with lymph node invasion (P = 0.004) and distant metastasis (P = 0.032). Importantly, FGF10 expression is an independent unfavorable prognostic factor (P = 0.042). Moreover, FGF10 knockdown significantly decreased the migration of cultured gastric adenocarcinoma cells, suggesting that FGF10 could promote the invasion of gastric adenocarcinoma. In conclusion, FGF10 expression was identified as a poor prognostic biomarker in gastric adenocarcinoma, and FGF10 could promote the invasion of gastric cancer cells. We suggest that FGF10 could be a potential and promising drug target in gastric adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Fator 10 de Crescimento de Fibroblastos/metabolismo , Metástase Linfática/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Idoso , China , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Onco Targets Ther ; 8: 615-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25792845

RESUMO

BACKGROUND: The clinical significance of fibroblast growth factor 1 (FGF1) has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored. PATIENTS AND METHODS: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan-Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma. RESULTS: Higher FGF1 expression rate is 56.7% (101/178) in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001). Expression of FGF1 is significantly associated with lymph node invasion (P<0.001), distant metastasis (P=0.013), and differentiation (P=0.015). Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021), and can be identified to be an independent unfavorable prognostic factor (P=0.004). CONCLUSION: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.

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