0
[文章]

转录组相关研究(二)

RNA专题

英文题目:Independent effect of main components in particulate matter on DNA methylation and DNA methyltransferase: A molecular epidemiology study.

中文题目:颗粒物中主要成分对DNA甲基化和DNA甲基转移酶的独立影响:一项分子流行病学研究。

作者:Wang Y

作者单位:Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.中国疾病预防控制中心国家职业健康与毒物控制研究所化学安全与健康重点实验室(北京)

期刊:ENVIRONMENT INTERNATIONAL   发表时间:2019-11   IF = 8.58

DOI: 10.1016/j.envint.2019.105296

英文摘要:

BACKGROUND: There is a paucity of mechanistic information on the DNA methylation  and particulate matter (PM) exposure. This study aimed to investigate the association of PM and its component with DNA methylation, and the roles of DNA methyltransferase (DNMTs).

METHODS: There were 240 high-exposed, 318 low-exposed and 210 non-exposed participants in this study. Individual concentrations of PM, polycyclic aromatic  hydrocarbons (PAHs) and metals were identified by the monitoring data in their workplaces. Urinary 1-OHP and metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, DNMT3A and DNMT3B were measured. We used mediation analysis to evaluate the role of DNMTs expression on DNA methylation alteration induced by PAHs and metals components.

RESULTS: The decreasing trend of % 5mC was associated with increment of PM exposure in all subjects. We found that one IQR increase in total PAHs (3.82 μg/m3) and urinary 1-OHP (1.06 μmol/mol creatinine) were associated with a  separate 6.08% and 7.26% decrease in % 5mC (P = 0.009, P < 0.001), and one IQR increase in urinary Ni (27.75 μmol/mol creatinine) was associated with a 3.29% decrease in % 5mC (P = 0.03). The interaction of urinary 1-OHP with Ni on global  DNA methylation (%5mC) was not found (P interaction = 0.89). PM exposure was significantly associated with decreased mRNA level of DNMT3B, but the mediated effect of the PAHs and Ni levels on % 5mC through the DNMT3B pathway was not Observed. 

CONCLUSIONS: We found the decrement of global DNA methylation and DNMT3B expression with elevated PM levels in population. The independent mode of action  on DNA hypomethylation was found from PAHs and metal components. Global DNA hypomethylation might be a potential biomarker for evaluation of adverse health effects in response to PM exposure.

中文摘要:

背景:关于DNA甲基化和颗粒物(PM)暴露的机制信息非常缺乏。本研究旨在探讨PM及其组分与DNA甲基化的关系及DNA甲基转移酶(DNMTs)的作用。通过对其工作场所PM、多环芳烃(PAHs)和金属的监测数据,确定了PM、多环芳烃(PAHs)和金属的个体浓度。以尿1-OHP和金属元素为暴露指标。检测DNA甲基化率(5mC)及DNMT1DNMT3ADNMT3BmRNA表达。采用中介分析法研究DNMTs在多环芳烃和金属组分诱导DNA甲基化改变中的作用。我们发现,总PAHs3.82μg/m3)和尿1-OHP1.06μmol/mol肌酐)的一个IQR增加(3.82μg/m3)和尿1-OHP1.06μmol/mol肌酐)与a相关。5mCP =0.009P <0.001)的单独6.08%7.26%分别降低6.08%7.26%和尿Ni27.75μmol/mol肌酐)的一个IQR增加(27.75μmol/mol肌酐)与尿Ni27.75μmol/mol肌酐)的一个IQR增加(3.29%)和尿Ni增加(3.29%)与3.29%的降低(P =0.03条)。尿1-OHPNi的相互作用,未发现DNA甲基化(5mC)(P相互作用 = 0.89)。PM暴露与DNMT3BmRNA水平降低显著相关,而PAHsNi水平通过DNMT3B途径对%5mC的介导作用则不明显。结论:PM水平升高可导致群体DNA甲基化和DNMT3B表达降低。从多环芳烃和金属组分中发现DNA甲基化的独立作用方式。全球DNA低甲基化可能是评估PM暴露对健康不利影响的潜在生物标志物。

 

 

英文题目:Transcriptomic and proteomic approaches reveal biological basis of intraoperative radiotherapy-treated tumor bed modification in breast cancer patients: A pilot Study.

中文题目:转录组学和蛋白质组学方法揭示了乳腺癌患者术中放疗治疗肿瘤床改良的生物学基础:一项初步研究。

作者:Shahani M

作者单位:Cancer Research Center, Shahid Beheshti University of Medical Sciences,

Tehran, Iran.伊朗德黑兰沙希德·贝赫什蒂医学大学癌症研究中心,

期刊Journal of Proteomics 发表时间:2019-11    IF = 3.67

DOI: 10.1016/j.jprot.2019.103596

英文摘要:

AIM: Intraoperative electron Radiotherapy, herein referred to, as IOeRT is a novel approach in breast cancer (BC) treatment. This study designed to investigate short-term molecular effects of 12Gy as Boost versus 21Gy as Radical  dose of IOeRT using high throughput approaches. MATERIALS AND METHODS: Six BC patients as a pilot study were treated with IOeRT following two separate strategies, including Boost and Radical doses. Approximately 100 mg of tumor bed tissue retrieved from each patient (before IOeRT,immediately, 24 h post-treatment). mRNA sequencing also Isobaric tag for relative and absolute quantitation (iTRAQ) were performed to study the transcriptome and proteome profile of IOeRT-treated tumor bed. RESULTS: Using NGS, ~6 Giga base (GB) clean data per individual samples were generated. Moreover, by iTRAQ for proteome quantification, in total, 1,045,410 spectrums were generated, likewise 5860 proteins were identified (FDR <0.01). CONCLUSION: Functional annotation and gene ontology (GO) indicated that significant enrichment in molecular pathways on BC treatment is somehow single high dose-independent. This means that, key molecular pathways in radiotherapy (RT) are equally enriched by both Boost and Radical doses. Generally, by modification of the Radical dose, with the same effectiveness, it is possible to  reduce single high dose irradiation in BC.

 

中文摘要:

目的:术中电子放射治疗(简称IOeRT)是治疗乳腺癌的一种新方法。本研究旨在研究12Gy作为促进剂和21Gy作为自由基的短期分子效应。采用高通量方法的IOeRT剂量。材料和方法:6BC患者作为一个试点研究,采用IOeRT治疗。遵循两种不同的策略,包括升压和自由基剂量,从每个患者(IOeRT,立即,24小时后处理)检索到大约100毫克的肿瘤床组织。采用相对和绝对定量法(iTRAQ)对IOeRT治疗的肿瘤床进行mRNA测序和等压标记,研究其转录组和蛋白质组分布。此外,通过iTRAQ进行蛋白质组定量,共产生1045410个蛋白质谱,鉴定5860个蛋白质(FDR<0.01)。结论:功能注释和基因本体(GO)表明,BC治疗的分子途径的显著富集是单剂量、高剂量无关的。这意味着,放射治疗中的关键分子途径(RT)同样被增强剂量和自由基剂量所丰富。一般来说,通过改变自由基剂量,以同样的效果,可以减少单次大剂量照射。

 

 

英文题目:The androgen receptor expression and association with patient\'s survival in

different cancers.

中文题目:不同癌症中雄激素受体的表达及其与患者生存的关系。

作者:Hu C

作者单位:State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China;南京医科大学生殖医学国家重点实验室

期刊: Genomics.     发表时间:2019-11   IF = 2.284

DOI: 10.1016/j.ygeno.2019.11.005

英文摘要:

To understand the androgen receptor (AR) in different human malignancies, we conducted a pan-cancer analysis of AR in different tumor tissues and association  with patient survival and obtained AR expression data from The Cancer Genome Atlas. Pan-Cancer Analysis of AR indicated that 12 tumor types had decreased AR expression in the tumor, while glioblastoma multiforme has overexpressed AR. The  survival analysis showed that high AR mRNA is associated with poor survival of stomach adenocarcinoma and low-grade glioma, but better survival of adrenocortical carcinoma, kidney renal clear cell carcinoma, acute myeloid leukemia, liver hepatocellular carcinoma, ovarian serous cystadenocarcinoma, and  skin cutaneous melanoma based on AR mRNA, protein or AR-score. AR was associated  with different clinical characteristics and AR correlated genes enriched in cancer-related pathways. These data indicate that AR signaling may be strongly associated with some cancer development and patients\' survival, which is promising for potential treatment using antiandrogen therapies.

中文摘要:

为了了解不同人类恶性肿瘤中的雄激素受体(AR),我们对不同肿瘤组织中的AR进行了泛癌分析,并与患者生存率进行了关联,获得了癌症基因组图谱中AR的表达数据。全癌AR分析显示,12种肿瘤类型AR表达降低,而多形性胶质母细胞瘤AR表达升高。生存分析表明,高AR mRNA与胃癌和低级别胶质瘤的生存率低有关,但与肾上腺皮质癌的生存率高有关,肾肾透明细胞癌、急性髓细胞性白血病、肝细胞癌、卵巢浆液性囊腺癌和皮肤黑色素瘤(基于AR mRNA、蛋白质或AR评分)。AR与不同的临床特征有关,AR相关基因在肿瘤相关途径中丰富。这些数据表明AR信号可能与某些癌症的发展和患者的生存密切相关,这对抗雄激素治疗具有潜在的应用前景。

 

 

英文题目:Activation of NLRP3 inflammasome by lymphocytic microparticles via TLR4 pathway contributes to airway inflammation.

中文题目:淋巴细胞微粒通过TLR4途径激活NLRP3炎症小体。有助于气道炎症。

作者:Qiu Q

作者单位:Department of Geriatrics, First Affiliated Hospital, Army Medical University, Chongqing, 400038, China; Research Institute of Tuberculosis, Chongqing Public Health Medical Center, Chongqing, 400036, China.陆军医科大学第一附属医院老年科

期刊:EXPERIMENTAL CELL RESEARCH 发表时间:2019-11  IF = 3.21

DOI: 10.1016/j.yexcr.2019.111737

英文摘要:

The presence of elevated T lymphocytic microparticles (TLMPs) during respiratory  illness is associated with airway and lung inflammation and epithelial injuries.  Although inflammasome and IL-1β signaling are crucial in airway inflammation, little was known about their regulatory mechanism. We hypothesized that TLMPs trigger inflammasome activation and IL-1β production in bronchial and alveolar epithelial cells to induce airway and lung inflammation. In this study, TLMPs induced IL-1β and IL-18 secretion through NLRP3 inflammasome activation and upregulated TLR4 mRNA and protein expression in alveolar (A549) and human airway  epithelial (16HBE) cells. Pretreatment with CLI-095, a specific inhibitor of TLR4 signaling, dramatically diminished the TLMP-induced release of IL-1β and IL-18 by inhibiting the formation of NLRP3/ASC/pro-caspase-1 inflammasome in a dose-dependent manner. The TLMP-induced autophagy inhibition in epithelial cells  was dependent on the PI3K/Akt signaling pathway, which significantly increased NLRP3 expression and enhanced TLMP-induced inflammation. TLR4, IL-1β, and IL-18 proteins harbored in TLMPs were nonessential for the pro-inflammatory effect. In  conclusion, TLMPs induce bronchial and alveolar epithelial cell secretion of IL-1β and IL-18 cytokines by activating the TLR4 and PI3K/Akt signaling pathways  and inhibiting autophagy. These effects lead to NLRP3 inflammasome formation and accumulation. TLMPs may be regarded as deleterious markers of airway and lung damage in respiratory diseases.

中文摘要:

呼吸过程中T淋巴细胞微粒(TLMPs)升高。疾病与气道和肺部炎症和上皮损伤有关。虽然炎症小体和IL-1β信号在气道炎症中起着关键作用,但其调节机制尚不清楚。我们假设TLMPs在支气管和肺泡上皮细胞中激活炎症小体和产生IL-1β,从而诱导气道和肺部炎症。在本研究中,TLMPs通过NLRP3炎症激活诱导IL-1βIL-18分泌,上调肺泡(A549)和人气道上皮(16HBE)细胞TLR4 mRNA和蛋白表达。TLR4信号传导的特异性抑制剂CLI-095预处理通过抑制NLRP3/ASC/pro-caspase-1炎症小体的形成,显著降低TLMP诱导的IL-1βIL-18的释放。TLMP对上皮细胞自噬的抑制作用依赖于PI3K/Akt信号通路,而PI3K/Akt信号通路显著增加了NLRP3的表达,增强了TLMP诱导的炎症反应。TLR4IL-1βIL-18蛋白在TLMPs中的表达对促炎作用不重要。总之,TLMPs通过激活TLR4PI3K/Akt信号通路,抑制自噬,诱导支气管和肺泡上皮细胞分泌IL-1βIL-18细胞因子。这些作用导致NLRP3炎症小体的形成和积聚。TLMPs可作为呼吸道疾病中气道和肺损伤的有害标志物。

 

 

英文题目:PKD deletion promotes autophagy and inhibits hypertrophy in cardiomyocyte.

中文题目:PKD缺失促进心肌细胞自噬,抑制心肌细胞肥大。

作者:Zhao D

作者单位:Shandong University of Traditional Chinese Medicine, Postdoctoral Station, Shandong, China; 山东中医药大学博士后站

期刊:EXPERIMENTAL CELL RESEARCH   发表时间:2019-11  IF = 3.21

DOI: 10.1016/j.yexcr.2019.111742

英文摘要:

Protein kinase D (PKD) plays an important role in the development of cardiac hypertrophy induced by pressure overload. However, the mechanism involved is unclear. This study, using primary cardiomyocyte culture, PKD knockdown and overexpression, and other molecular techniques, tested our hypothesis that PKD pathway mediates cardiac hypertrophy by negatively regulating autophagy in cardiomyocyte. Neonatal cardiomyocytes were isolated from Wistar rats and cell hypertrophy was induced by norepinephrine treatment (PE, 10-4 mol/L), and divided into the following groups: (1) Vehicle; (2) PE; (3) PE + control siRNA; (4) PE + Rapamycin (100 nM); (5) PE + PKD-siRNA (2 × 108 U/0.1 ml); (6) PE + PKD siRNA + 3 MA (10 mM). The results showed that PE treatment induced cardiomyocyte hypertrophy, which were confirmed by cell size and biomarkers of cardiomyocyte hypertrophy including increased ANP and BNP mRNA. PKD knockdown or Rapamycin significantly inhibited PE-induced cardiomyocyte hypertrophy. In addition, PKD siRNA increased autophagy activity determined by electron microscopy, increased biomarkers of autophagy by Western blot, accompanied by down-regulated AKT/mTOR/S6K pathway. All the effects of PKD knockout were inhibited by co-treatment with 3-MA, an autophagy inhibitor. Oppositely, the autophagy in cardiomyocytes was inhibited by PKD overexpression. These results suggest that PKD participates in the development of cardiac hypertrophy by regulating autophagy via AKT/mTOR/S6K pathway.

中文摘要:

蛋白激酶DPKD)在压力超负荷引起的心肌肥厚中起重要作用。然而,其机制尚不清楚。本研究利用原代心肌细胞培养、PKD基因敲除和过表达等分子技术,验证了PKD途径通过负性调节心肌细胞自噬介导心肌肥大的假说。从Wistar大鼠心肌细胞中分离出心肌细胞,用去甲肾上腺素(PE10-4 mol/L)诱导心肌细胞肥大,分为以下组:(1)载体组;(2PE组;(3PE+对照siRNA组;(4PE+雷帕霉素组(100nm);(5PE+PKD-siRNA组(2×108u/0.1ml);(6PE+PKD.siRNA+3ma10mm)。结果表明,PE可诱导心肌细胞肥大,心肌细胞的大小和心肌细胞的生物标志物证实了PE可诱导心肌细胞肥大,包括ANPBNP mRNA的升高。PKD基因敲除或雷帕霉素显著抑制PE诱导的心肌细胞肥大。此外,PKD.siRNA增强了电镜下自噬活性,Western blot检测自噬生物标志物增加,并伴有下调的AKT/mTOR/S6K途径。与自噬抑制剂3-MA联合治疗可抑制PKD基因敲除。相反,PKD过表达抑制心肌细胞自噬。提示PKD通过AKT/mTOR/S6K途径调节自噬参与心肌肥厚的发生。

Hello ATCG 2019-11-27 18:04:51

0个评论

    暂时还没有评论!

热门话题