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Coordinated transcription of ANRIL and P16 genes is silenced by P16 DNA methylation 被引量:2
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作者 Ying Gan Wanru Ma +5 位作者 Xiuhong Wang Juanli Qiao Baozhen Zhang Chenghua Cui Zhaojun Liu Dajun Deng 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2018年第1期93-103,共11页
Objective: To investigate the relationship between the transcription of ANRIL, P15, P14 and P16 at the same locus and the regulation mechanism of ANRIL.Methods: Publicly available database of Cancer Cell Line Encycl... Objective: To investigate the relationship between the transcription of ANRIL, P15, P14 and P16 at the same locus and the regulation mechanism of ANRIL.Methods: Publicly available database of Cancer Cell Line Encyclopedia(CCLE) was used in bioinformatic analyses. Methylation of Cp G islands was detected by denaturing high performance liquid chromatography(DHPLC). Gene transcript levels were determined using quantitative real-time polymerase chain reaction(q RTPCR) assays. An engineered P16-specific transcription factor and DNA methyltransferase were used to induce P16-specific DNA demethylation and methylation.Results: The expression level of ANRIL was positively and significantly correlated with that of P16 but not with that of P15 in the CCLE database. This was confirmed in human cell lines and patient colon tissue samples. In addition, ANRIL was significantly upregulated in colon cancer tissues. Transcription of ANRIL and P16 was observed only in cell lines in which the P16 alleles were unmethylated and not in cell lines with fully methylated P16 alleles.Notably, P16-specific methylation significantly decreased transcription of P16 and ANRIL in BGC823 and GES1 cells. In contrast, P16-specific demethylation re-activated transcription of ANRIL and P16 in H1299 cells(P〈0.001).Alteration of ANRIL expression was not induced by P16 expression changes.Conclusions: ANRIL and P16 are coordinately transcribed in human cells and regulated by the methylation status of the P16 Cp G islands around the transcription start site. 展开更多
关键词 ANRIL p16 CpG island DNA methylation transcriptional regulation
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EXPRESSION OF P16 AND CYCLIN D1 IN THE COURSE OFCARCINOGENESIS OF THE STOMACH
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作者 陈玉龙 徐峰 李燕杰 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1999年第1期29-31,共3页
Objective: To determine p16 and cyclin D1 expression in the specimen of gastric carcinoma, atypic hyperplasia, atrophic gastritis, superficial gastritis and normal gastric mucosa. Methods: Using immunohistochemical me... Objective: To determine p16 and cyclin D1 expression in the specimen of gastric carcinoma, atypic hyperplasia, atrophic gastritis, superficial gastritis and normal gastric mucosa. Methods: Using immunohistochemical method (ABC), the samples of 58 adenocarcinomas, 22 atypic hyperplasias, 28 atrophic gastritis, 27 superficial gastritis and 15 gastric epitheliums were analyzed. Results: Positive immunostaining rate for p16 protein was the highest in normal gastric mucosa and decreased with the lesions progressing from superficial gastritis to atrophic gastritis to atypital hyperplasia and to adenocarcinoma (85%, 78.6%, 31.8%, 48.3% respectively); Positive immunostaining of cyclin D1 can observed in atrophic gastritis. With the lesions progressing from atrophic gastritis to atypical hyperplasia to adenocarcinoma, its expression rate increased (17.9%, 36.4%, 53.4% respectively), and there was a significant difference between adenocarcinoma and atrophic gastritis group (P<0.05). An interesting observation was that inverse expression between p16 and cyclin D1, was shown in most of gastric cancer detected. Conclusion: It is indicated that p16 and cyclin D1 play an important role in the gastric carcinogenesis, the inverse expression between p16 and cyclin D1 suggested that there is a suppression trend in them. 展开更多
关键词 p16 Cyclin D1 Gastric carcinoma CARCINOgenesIS
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The correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue
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作者 Lai-Fang Zhu 《Journal of Hainan Medical University》 2017年第8期130-133,共4页
Objective:To study the correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue.Methods:A total of 78 patients with cervical cancer who were ... Objective:To study the correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue.Methods:A total of 78 patients with cervical cancer who were treated in our hospital between August 2013 and May 2016 were collected as the observation group, and patients with cervicitis who received examination in our hospital during the same period were selected as the control group. The cervical secretions were collected to determine p16, MMP-2, MMP-7 and MMP-9 levels with enzyme-linked immunosorbent assay (ELISA) kit, cervical lesion tissue samples were collected to determine angiogenesis index levels by RIA method, and ELISA kits were used to determine proliferation genes B7-H4, GBP1, Sp2, EZH2 and PKC protein expression. Pearson test was used to analyze the correlation of p16 and MMPs expression in cervical secretions with the angiogenesis and cell proliferation in cervical cancer tissue of patients with cervical cancer.Results: p16, MMP-2, MMP-7 and MMP-9 levels in cervical secretions of observation group were higher than those of control group, and COX-2, VEGFA, VEGFC, B7-H4, Sp2, EZH2 and PKC expression in cervical biopsy tissue were higher than those of control group while GBP1 expression was lower than that of control group.Conclusion:p16 and MMPs expression in cervical secretions of patients with cervical cancer can quantifiably reflect the degree of angiogenesis and proliferation of cervical cancer cells. 展开更多
关键词 CERVICAL cancer p16 Matrix METALLOPROTEINASE ANGIOgenesIS Cell proliferation
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Association of low p16INK4a and p15INK4b mRNAs expression with their CpG islands methylation with human hepatocellular carcinogenesis 被引量:22
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作者 YangQin Jian-YuLiu +2 位作者 BoLi Zhi-LinSun Ze-FangSun 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第9期1276-1280,共5页
AIM:To study the significance of p16 and p15 transcription suppression with hypermethylation of their genes′5′CpG islands during human hepatocellular carcinogenesis.METHODS:The mRNA expression levels of p16 and p15 ... AIM:To study the significance of p16 and p15 transcription suppression with hypermethylation of their genes′5′CpG islands during human hepatocellular carcinogenesis.METHODS:The mRNA expression levels of p16 and p15 genes were evaluated in cancerous,para-cancerous and non-cancerous tissues of 20 HCC,3 normal liver tissues from 3 accidentally died healthy adults using simi-quantitatively Northerm blot.The methylation status was also assessed with methylation specfic PCR.RESULTS:p16 mRNA expression level was decressed in the cancerous tissues in 60%(12/20) of HCC patients,of which 2 cases had no p16 mRNA detected,5 cases(25%) displayed variation in the order of cancerous<para-cancerous<non-cancerous liver tissues.p15 mRNA expression level was decreased in the cancerous tissues in 50%(10/20) HCC patients,of which one case had no p15 mRNA detected,4 cases (20%) displayed variation in the order of cancerous<para-cancerous<non-cancerous liver tissues.In cancerous,para-cancerous and non-cancerous tissues,p16 promoter CpG islands hypernethylation occurred 65% ,60% and 35%,while p15 promoter CpG islands hypermethylation occurred 50%,40% and 25%.of 12 HCCs with lower p16 promoter CpG islands methylation(91.6%).Hundred percent(10/10) HCCs with lower p15 mRNA expression level showed p15 promoter CpG islands methylation.Significant correlation between 5′CpG islands methylation and p16/p15 mRNA expression suppression was found.The dexreased expression of p16/p15 mRNA or metyylation of p16.p15 promoters 5′CpG island was significantly,0.01.2,0.00271,0.0218,respectively,(p<0.05).CONCLUSION:p16 and p15 genes transcriptional inactivation might play an important role in hepataocarcinogenesis.5′CpG islands methylation might bi the major mechanism of p16 and p15 genes inactivation in primary HCC in the studied population.5′CpG islands methylation of p16 and p15 genes might be an early event in hepatocarcinogenesis. 展开更多
关键词 肝细胞癌 CPG岛甲基化 肿瘤发生 p16基因 P15基因
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CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16INK4a 被引量:3
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作者 Wenqi Du Zongxiang Liu +5 位作者 Wentao Zhu Tongtong Li Zhiman Zhu Lulu Wei Jun Song Dongsheng Pei 《Cancer Biology & Medicine》 SCIE CAS CSCD 2019年第3期514-529,共16页
Objective: CSN6 is a vital subunit of the constitutive photomorphogenesis 9(COP9) signalosome(CSN), which is responsible for development disorders and promotes ubiquitin-26 S proteasome-dependent degradation in vitro ... Objective: CSN6 is a vital subunit of the constitutive photomorphogenesis 9(COP9) signalosome(CSN), which is responsible for development disorders and promotes ubiquitin-26 S proteasome-dependent degradation in vitro and vivo.Its role in the tumor development of gastric cancer remains unclear.In this study, we investigated the role of CSN6 in gastric cancer progression.Methods: Human gastric cancer samples were collected and immunohistochemistry was performed to identify the role of CSN6 in gastric cancer.The cell proliferation was measured by CCK-8 and the EdU incorporation method.Immunofluorescence localization and a co-immunoprecipitation study were used to show the interaction between the protein CSN6 and p16.Ubiquitination assay was performed to validate whether ubiquitination is involved in CSN6-mediated p16 degradation.BALB/c nude mice were used to produce a tumor model in order to test the effect of CSN6 on cancer growth in vivo.Results: CSN6 expression was dramatically increased in gastric cancer tissues compared with paired adjacent non-tumor tissues and CSN6 was correlated with worse overall and disease-specific survival.Additionally, we also found that CSN6 downregulated p16 protein expression, thereby promoting gastric cancer cell growth and proliferation.Moreover, CSN6 interacted with p16 and a proteasome activator REGγ(PA28γ), thereby facilitating ubiquitin-independent degradation of p16.Conclusions: CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16. 展开更多
关键词 CSN6 GASTRIC cancer proliferation p16 REGγ
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Comethylation of p16 and MGMT genes in colorectal carcinoma:Correlation with clinicopathological features and prognostic value 被引量:10
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作者 Koviljka Krtolica Milena Krajnovic +3 位作者 Slavica Usaj-Knezevic Dragan Babic Dusan Jovanovic Bogomir Dimitrijevic 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第8期1187-1194,共8页
AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT met... AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis. 展开更多
关键词 结直肠癌 p16基因 MGMT基因 共甲基化 临床病理特征 相关性
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METHYLATION OF p16 AND p15 GENES IN MULTIPLE MYELOMA
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作者 陈文明 吴垠 +3 位作者 朱嘉芷 刘敬忠 谭淑珍 夏成青 《Chinese Medical Sciences Journal》 CAS CSCD 2002年第2期101-105,共5页
Objective.To investigate the frequency of p16a nd p15gene methylation in multiple myeloma (MM),and its relationship with bone marrow ce ll apoptosis and clinical outcome.Methods.Twenty-two patients with MM were stu di... Objective.To investigate the frequency of p16a nd p15gene methylation in multiple myeloma (MM),and its relationship with bone marrow ce ll apoptosis and clinical outcome.Methods.Twenty-two patients with MM were stu died to detect p16and p15gene methylation.Methyla-tion-specific polymerase chain rea ction(MSP)was used to detect gene methylation,and terminal trans-ferase-mediated dUTP nick end-labeling(TUNEL)was used to detect cell apoptosis.Results.p16and /or p15gene methylatoin was d etected in 10of 22patients(45.4%).There were 3pa-tients with p16gene methylation,9p atients with p15gene methylation,a nd 2patients with both genes methyla-tion.The incidence of methylation o f p15gene was higher than that of p16g ene(P<0.05).The patients with p16and /or p15gene methylation had a delayed cell apoptosis,poor respon se to chemotherapy,and a short over-all survival(OS).Conclusion.The methylation of p16and /or p15gen e plays a key role in MM apoptosis path ogenesis.The patients with both p16and p15gene me thylation had a poor prognosis. 展开更多
关键词 多发怀骨髓瘤 p16基因 P15基因 甲基化 骨髓细胞凋亡
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Study on p16^(INK4a) and p15^(INK4b) genes of human bronchial epithelial cells malignantly transformed bycyclophosphamide and thiotepa
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作者 Cheng Guangyu +2 位作者 Ma Huazhi 《癌变.畸变.突变》 CAS CSCD 2001年第4期231-231,共1页
关键词 支气管上皮细胞 恶性转化 环磷酰胺 硫特普 p16^INK4A P15^INK4B
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CO-DELETION OF BOTH p15/p16 GENES CORRELATES WITH POOR PROGNOSIS NON-SMALL CELL LUNG CNACER
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作者 胡颖 廖美琳 +2 位作者 丁嘉安 周瑾 许凯黎 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2002年第3期216-219,共4页
Objective: To investigate the relationship between co-deletion of p15/p16 genes and the prognostic significance in patients with non-small cell lung cancer (NSCLC). Methods: By using polymerase chain reaction (PCR), t... Objective: To investigate the relationship between co-deletion of p15/p16 genes and the prognostic significance in patients with non-small cell lung cancer (NSCLC). Methods: By using polymerase chain reaction (PCR), the loss of p15/p16 genes was examined in DNA samples from 140 NSCLC patients. Results: The rate of co-deletion in adenocarcinoma was significantly higher than that in squamous cell carcinoma (P<0.05), while it was not related to sex, age and TNM stages (P>0.05). By a five years’ follow-up survey, the survival rate of NSCLC patients with co-deletion of p15/p16 genes was obviously lower than that of patients without co-deletion (P<0.01). In the multivariate analysis, co-deletion of p15/p16 genes and TNM stages were identified as independent predictors for overall survival (P<0.01). Conclusion: Since the co-deletion of p15/p16 genes is significantly related to the prognosis of NSCLC patients, detecting co-deletion of both genes might be used as a potential marker for NSCLC prognosis. 展开更多
关键词 No-small cell lung cancer Co-deletion P15 p16 PROGNOSIS
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Role of p53 suppression in the pathogenesis of hepatocellular carcinoma 被引量:2
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作者 Heena B Choudhary Satish K Mandlik Deepa S Mandlik 《World Journal of Gastrointestinal Pathophysiology》 2023年第3期46-70,共25页
In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrho... In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC. 展开更多
关键词 Hepatocellular carcinoma P53 Tumour suppressor gene Murine double minute 2 CHEMORESISTANCE
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Study of pathogenic genes in a pedigree with familial dilated cardiomyopathy
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作者 Xin-Ru Zhang Hang Ren +2 位作者 Fang Yao Yang Liu Chun-Li Song 《World Journal of Clinical Cases》 SCIE 2023年第11期2412-2422,共11页
BACKGROUND Dilated cardiomyopathy(DCM)is a genetically heterogeneous cardiac disorder characterized by left ventricular dilation and contractile dysfunction.The substantial genetic heterogeneity evident in patients wi... BACKGROUND Dilated cardiomyopathy(DCM)is a genetically heterogeneous cardiac disorder characterized by left ventricular dilation and contractile dysfunction.The substantial genetic heterogeneity evident in patients with DCM contributes to variable disease severity and complicates overall prognosis,which can be very poor.AIM To identify pathogenic genes in DCM through pedigree analysis.METHODS Our research team identified a patient with DCM in the clinic.Through invest-igation,we found that the family of this patient has a typical DCM pedigree.High-throughput sequencing technology,next-generation sequencing,was used to sequence the whole exomes of seven samples in the pedigree.RESULTS A novel and potentially pathogenic gene mutation-ANK2p.F3067L-was discovered.The mutation was completely consistent with the clinical information for this DCM pedigree.Sanger sequencing was used to further verify the locus of the mutation in pedigree samples.These results were consistent with those of high-throughput sequencing.CONCLUSIONS ANK2p.F3067L is considered a novel and potentially pathogenic gene mutation in DCM. 展开更多
关键词 Dilated cardiomyopathy Gene mutation Whole exomes sequencing Sanger sequencing ANK2p.F3067L Potentially pathogenic gene
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Changes of p53 and Waf1p21 and cell proliferation in esophageal carcinogenesis 被引量:13
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作者 WANG Li Dong 1, YANG Wan Cai 1, ZHOU Qi 1, XING Ying 1,JIA Yun Ying 2 and ZHAO Xin 1 《World Journal of Gastroenterology》 SCIE CAS CSCD 1997年第2期30-32,共3页
Changesofp53andWaf1p21andcelproliferationinesophagealcarcinogenesisWANGLiDong1,YANGWanCai1,ZHOUQi1,XINGYi... Changesofp53andWaf1p21andcelproliferationinesophagealcarcinogenesisWANGLiDong1,YANGWanCai1,ZHOUQi1,XINGYing1,JIAYunYing2a... 展开更多
关键词 ESOPHAGEAL neoplasms PRECANCEROUS conditions P53 genes Waf1p21 genes suppressor tumor
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Relationship between alterations of p16^( INK4a) and p14^(ARF) genes of CDKN2A locus and gastric carcinogenesis 被引量:8
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作者 汤绍辉 罗和生 +2 位作者 于皆平 杨冬华 舒建昌 《Chinese Medical Journal》 SCIE CAS CSCD 2003年第7期1083-1087,共5页
Objective To investigate the relationship between alterations of p16 INK4a and p14 ARF genes and gastric carcinogenesis Methods The tumors and neighboring gastric tissues from 48 patients with gastric ca... Objective To investigate the relationship between alterations of p16 INK4a and p14 ARF genes and gastric carcinogenesis Methods The tumors and neighboring gastric tissues from 48 patients with gastric cancer were studied The homozygous deletion, mutation, methylation of the CpG islands, and mRNA expression of p16 INK4a and p14 ARF genes were assessed by PCR, PCR SSCP, PCR based methylation assay, and RT PCR Results ① The homozygous deletion rate of p16 INK4a and p14 ARF was 35 4% (17/48), and no homozygous deletion was examined in any gastric tissue neighboring the tumor ② There was no point mutation of p16 INK4a and p14 ARF in 31 gastric cancers without homozygous deletion or in the matched gastric tissues adjacent to the tumor ③ Methylation of the CpG islands of p16 INK4a and p14 ARF was detected in 47 9% (23/48) of gastric cancers, while methylation was observed only in 2 of 48 gastric tissues neighboring the cancer with a significant difference ( P <0 01) ④ The loss rate of p16 INK4a mRNA was 47 9% (23/48) in gastric cancer, and the patients of the combined methylation of exons 1α and 2 had a higher loss rate (100%, 6/6) of p16 INK4a mRNA than those of the methylation of the other exons (11 8%, 2/17, P <0 01); the loss rate of p14 ARF mRNA was 45 8%(22/48) in gastric cancer, and patients with the combined methylation of exons 1β and 2 had a higher loss rate (100%, 3/3) of p14 ARF mRNA than those of the methylation of the other exons (15%, 3/20, P <0 05) ⑤ The combined loss of p16 INK4a and p14 ARF mRNAs was examined in 1 (5 6%) of 18 patients of well and moderately differentiated carcinomas, and 11 (36 7%) of 30 patients of poorly and not differentiated carcinomas with a significant difference ( P <0 05) Conclusion p16 INK4a and p14 ARF genes are frequently inactivated by homozygous deletion and methylation of the 5'CpG islands in gastric cancer, which may play an important role in the carcinogenesis of gastric cancer 展开更多
关键词 stomach neoplasms · p16 INK4a gene · p14 ARF gene · carcinogenesis
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Genes for RNA-binding proteins involved in neuralspecific functions and diseases are downregulated in Rubinstein-Taybi iNeurons 被引量:2
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作者 Lidia Larizza Luciano Calzari +1 位作者 Valentina Alari Silvia Russo 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第1期5-14,共10页
Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the ... Taking advantage of the fast-growing knowledge of RNA-binding proteins(RBPs)we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons(iNeurons)modelling the neurodevelopmental Rubinstein Taybi Syndrome(RSTS)caused by mutations in the genes encoding CBP/p300 acetyltransferases.We discuss top and functionally connected downregulated genes sorted to“RNA processing”and“Ribonucleoprotein complex biogenesis”Gene Ontology clusters.The first set of downregulated RBPs includes members of hnRNHP(A1,A2B1,D,G,H2-H1,MAGOHB,PAPBC),core subunits of U small nuclear ribonucleoproteins and Serine-Arginine splicing regulators families,acting in precursor messenger RNA alternative splicing and processing.Consistent with literature findings on reduced transcript levels of serine/arginine repetitive matrix 4(SRRM4)protein,the main regulator of the neural-specific microexons splicing program upon depletion of Ep300 and Crebbp in mouse neurons,RSTS iNeurons show downregulated genes for proteins impacting this network.We link downregulated genes to neurological disorders including the new HNRNPH1-related intellectual disability syndrome with clinical overlap to RSTS.The set of downregulated genes for Ribosome biogenesis includes several components of ribosomal subunits and nucleolar proteins,such NOP58 and fibrillarin that form complexes with snoRNAs with a central role in guiding post-transcriptional modifications needed for rRNA maturation.These nucleolar proteins are“dual”players as fibrillarin is also required for epigenetic regulation of ribosomal genes and conversely NOP58-associated snoRNA levels are under the control of NOP58 interactor BMAL1,a transcriptional regulator of the circadian rhythm.Additional downregulated genes for“dual specificity”RBPs such as RUVBL1 and METTL1 highlight the links between chromatin and the RBP-ome and the contribution of perturbations in their cross-talk to RSTS.We underline the hub position of CBP/p300 in chromatin regulation,the impact of its defect on neurons’post-transcriptional regulation of gene expression and the potential use of epidrugs in therapeutics of RBP-caused neurodevelopmental disorders. 展开更多
关键词 alternative splicing CBP/p300 chromatin regulators downregulated genes induced pluripotent stem cell-neurons neurodevelopmental disorders ribosome biogenesis RNA-binding proteins RNASEQ Rubinstein-Taybi
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Study on the Function of ORF Genes of Porcine Circovirus-like Virus P1
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作者 Libin WEN Xuejiao ZHU +2 位作者 Qi XIAO Wei WANG Kongwang HE 《Agricultural Biotechnology》 CAS 2021年第2期84-88,92,共6页
[Objectives]This study was conducted to determine the functions of eight ORF genes of porcine circovirus-like virus P1.[Methods]The double-copy tandem molecular cloning of porcine circovirus-like virus P1 genome was u... [Objectives]This study was conducted to determine the functions of eight ORF genes of porcine circovirus-like virus P1.[Methods]The double-copy tandem molecular cloning of porcine circovirus-like virus P1 genome was used to construct molecular clones with eight ORFs deleted by DNA site-directed mutagenesis technology.After transfected into PK15 cells for a certain period of time,RNA were extracted and was used to verify whether the eight ORFs were deleted or not and used for gene microarry analysis.The GO functions and KEGG pathway enrichment of differentially expressed genes were analyzed.[Results]P1 ORF1 is mainly involved in the biological processes of defense response to virus,signal transduction,regulation of Rab GTPase activity,and lipid metabolic process,and involved in the molecular functions of protein phosphatase inhibitor activity,phosphatidylinositol phospholipase C activity,2 iron,2 sulfur cluster binding,phosphoric diester hydrolase activity,and Rab GTPase activator activity,and in the KEGG pathways of secretion of digestive gland and nervous system development.P1 ORF2 is mainly involved in the biological processes of positive regulation of leukocyte chemotaxis,positive regulation of cell proliferation,positive regulation of cell migration,defense response to virus,regulation of cell growth,and involved in the molecular functions of insulin-like growth factor binding,and chemokine activity,and in the KEGG pathways of cytosolic DNA-sensing pathway,RIG-I-like receptor signaling pathway,toll-like receptor signaling pathway,chemokine signaling pathway,and cytokines,cytokine-cytokine receptor interaction.The biological processes,molecular functions and related pathways involving P1 ORF3 and ORF5 are basically similar to those of ORF2.P1 ORF8 is mainly involved in the biological processes of purine ribonucleotide biosynthetic process,amino acid transport,defense response to virus,amino acid transmembrane transport,and involved in molecular functions of N6-(1,2-dicarboxyethyl)AMP AMP-lyase(fumarate-forming)activity,iron-sulfur cluster binding,amino acid transmembrane transporter activity.[Conclusions]The analysis of the ORF functions of P1 virus lays a foundation for the study of its pathogenicity and pathogenesis. 展开更多
关键词 Porcine circovirus-like virus P1 Function of ORF genes MICROARRAY Differentially expressed genes
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Effect of 5-Aza-2'-deoxycytidine on the P16 tumor suppressor gene in hepatocellular carcinoma cell line HepG2 被引量:21
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作者 Li Hua Liu1 Wen Hua Xiao2 Wei Wen Liu3 1Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China (now working in Department of Gastroenterology, General Hospital of PLA, Lanzhou 730050, Gansu Province, China)2Department of Oncology3Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第1期131-135,共5页
INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecula... INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecular mechanisms of hepatocarcinogenesisremain poorly understood, an increasing number ofgenetic abnormalities have been recognized[7-10],for example, the p16 gene[11,12] the p53gene[13-18], the E-cadherin gene[19], and the c-mycgene[20]. 展开更多
关键词 liver neoplasms genes p16 methylation genes suppressor tumor flow CYTOMETRY immunohistochemistry polymerase chain reaction
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非小细胞肺癌p14^(ARF) p16^(INK4a)蛋白共表达及其临床意义 被引量:6
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作者 李军果 胡义德 +5 位作者 叶明福 谢启超 高丽莉 孙玉兰 杨永峰 钱海洪 《中国肿瘤临床》 CAS CSCD 北大核心 2005年第18期1021-1024,共4页
目的:探讨p14ARF、p16INK4a蛋白在非小细胞肺癌(NSCLC)组织中的表达、意义及相关关系。方法:采用免疫组织化学SP方法对103例NSCLC组织中p14ARF和p16INK4a蛋白的表达进行检测。结果:103例NSCLC组织中p14ARF、p16INK4a蛋白表达阴性率分别... 目的:探讨p14ARF、p16INK4a蛋白在非小细胞肺癌(NSCLC)组织中的表达、意义及相关关系。方法:采用免疫组织化学SP方法对103例NSCLC组织中p14ARF和p16INK4a蛋白的表达进行检测。结果:103例NSCLC组织中p14ARF、p16INK4a蛋白表达阴性率分别为70.87%和43.69%,差异有显著性(P<0.01)。其中35例p14ARF、p16INK4a蛋白表达共阴性,共阴性率达33.98%(35/103),鳞癌中共阴性率明显高于其它组织类型(P<0.01)。p14ARF、p16INK4a蛋白表达阴性相互间无显著相关性(P>0.05)。临床Ⅲ+Ⅳ期病例两种蛋白表达阴性率明显高于临床Ⅰ+Ⅱ期(P<0.05)。结论:NSCLC组织p14ARF、p16INK4a蛋白表达共阴性具有明显的组织学类型特异性,两种蛋白阴性表达是各自独立的事件。 展开更多
关键词 非小细胞肺癌 免疫组织化学 蛋白表达 P14^ARF p16^INK4A
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树舌多糖对小鼠HepA P16 P27 Rb基因表达的影响 被引量:5
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作者 王玉 于英君 +2 位作者 徐广有 王璐 周丽 《世界华人消化杂志》 CAS 2004年第6期1353-1356,共4页
目的:探讨树舌多糖抗肿瘤作用的机制. 方法:通过免疫组化、ELISA法分别测定瘤体和血清中抑癌基因P16,P27,Rb表达蛋白的量;通过透射电镜观察凋亡小体是否存在. 结果:树舌多糖作用后P16,P27,Rb基因表达蛋白的量与盐水组有差异具有统计学意... 目的:探讨树舌多糖抗肿瘤作用的机制. 方法:通过免疫组化、ELISA法分别测定瘤体和血清中抑癌基因P16,P27,Rb表达蛋白的量;通过透射电镜观察凋亡小体是否存在. 结果:树舌多糖作用后P16,P27,Rb基因表达蛋白的量与盐水组有差异具有统计学意义,免疫组化结果:bP<0.01, vs(1)(2);aP<0.05,vs(2)(3);dP<0.01,vs(3).ELISA结果: aP<0.05,vs(3);bP<0.01,cP<0.05,vs(4);dP<0.01,vs (3)(4);fp<0.01,vs(4);gP<0.05,hP<0.01,vs(3).且P16, P27表达的量与Rb呈负相关mr=-0.094(1),nr=-0.446 (1),再有观察到凋亡小体的存在. 结论:树舌多糖通过激活抑癌基因,抑制肿瘤的生长促进肿瘤细胞凋亡. 展开更多
关键词 树舌多糖 小鼠 HEPA p16 P27 RB基因表达 免疫组化 细胞周期
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新型抑癌基因 p16 被引量:12
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作者 朱如玮 刘振延 《肿瘤》 CAS CSCD 北大核心 1997年第3期178-179,共2页
新型抑癌基因p16朱如玮刘振延作者单位:苏州医学院病理解剖教研室(苏州215007)细胞的增殖失控是肿瘤组织最显著的特点,癌基因、抑癌基因对细胞增殖周期各环节直接或间接的调控作用发生异常,从而导致肿瘤的发生。近20年... 新型抑癌基因p16朱如玮刘振延作者单位:苏州医学院病理解剖教研室(苏州215007)细胞的增殖失控是肿瘤组织最显著的特点,癌基因、抑癌基因对细胞增殖周期各环节直接或间接的调控作用发生异常,从而导致肿瘤的发生。近20年来人们先后发现了十余种抑癌基因,其... 展开更多
关键词 肿瘤 抑癌基因 p16 控制
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Cyclin D1和 p16蛋白在胎儿心肌细胞中的表达 被引量:2
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作者 张光谋 徐振平 +2 位作者 井长勤 郭志坤 王鹏 《解剖学杂志》 CAS CSCD 北大核心 2006年第1期112-113,共2页
心肌细胞从胚胎期具有增殖能力的细胞成为成年期不具有增殖能力而只有发生肥大反应能力的过程中,存在增殖能力的变化和逐渐分化现象,该现象受细胞周期调控,细胞周期素(cyclin)是对细胞周期起正性调节作用的一类物质。p16蛋白是细... 心肌细胞从胚胎期具有增殖能力的细胞成为成年期不具有增殖能力而只有发生肥大反应能力的过程中,存在增殖能力的变化和逐渐分化现象,该现象受细胞周期调控,细胞周期素(cyclin)是对细胞周期起正性调节作用的一类物质。p16蛋白是细胞周期素依赖的蛋白激本科抑制因子(cyclin dependent kinase inhibitor,CKI)的一种, 展开更多
关键词 p16蛋白 心肌细胞 CYCLIN 细胞周期调控 细胞周期素 胎儿 增殖能力 CYCLIN p16蛋白 反应能力
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