最新研究进展揭示，抑癌基因功能的抑制或失活，除了与基因片段的丢失，DNA序列的错位、缺失、重组、变换、点突变等机制相关外，还与DNA序列中CpG岛（CpG island）中胞嘧啶（C）碱基环上发生的甲基化（^mCpG）有极其重要的相关性。RASS...最新研究进展揭示，抑癌基因功能的抑制或失活，除了与基因片段的丢失，DNA序列的错位、缺失、重组、变换、点突变等机制相关外，还与DNA序列中CpG岛（CpG island）中胞嘧啶（C）碱基环上发生的甲基化（^mCpG）有极其重要的相关性。RASSF1A基因（RAS association domain family 1 Agene）这一由Dammann等发现并命名的基因，在原发性肝癌中的表达情况则未有报道。展开更多
AIM： To investigate the role of transglutaminase 3 （TGM3） gene in human esophageal squamous cell carcinoma （ESCC）, and analyze its relationship with clinicopathological parameters. METHODS： Gene expression of TG...AIM： To investigate the role of transglutaminase 3 （TGM3） gene in human esophageal squamous cell carcinoma （ESCC）, and analyze its relationship with clinicopathological parameters. METHODS： Gene expression of TGM3 in fresh esophageal cancer tissues and their corresponding normal mucosas was detected immunohistochemically（I HC） by means of tissue microarray（TMA）. Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 10.0. RESULTS： Expression rate of TGM3 was reduced to 81.8% in ESCC. Expression of TGM3 was significantly inversely correlated with histological grade of esophageal carcinoma （in grade I, II and III tumors, the reduced expression was 4/7, 57/71, and 20/21, respectively, P 〈 0.05）, whereas it had no obvious correlations with lymph node metastasis and depth of invasion. CONCLUSION： Reduced expression of TGM3 may play an important role in esophageal carcinogenesis.展开更多
Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as...Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer ceils, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 （PRC2）. In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.展开更多
Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere m...Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere maintenance genes has been confirmed.Cumulative evidence shows that the difference of telomere length and stability among the individual depends on the genetic variants of telomere maintenance genes.Genetic variants in telomere maintenance genes may affect telomere length and stability,thus the increased cancer risk.This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.展开更多
Macrophage cells play an important role in the initiation and regulation of the immune response. All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids) affect a large number of biological pro...Macrophage cells play an important role in the initiation and regulation of the immune response. All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids) affect a large number of biological processes.Recently , retinoids have been shown promise in the therapy and prevention of various cancers. However, many interesting questions related to the activities of retinoids remain to be answered: (Ⅰ) Molecular mechanisms by which retinoids exert their effects; (Ⅱ) why the clinical uses of retinoids give undesirable side effects of varying severity with a higher freqllency of blood system symptoms; (Ⅲ)little is known for its impacts on macrophage cells etc. We set up this experiment, therefore, to examine the apoptosis of ATRA on macrophage Ana-1 cell line. Apoptosis of the cells was quantitated, after staining cells with propidium iodide (PI), by both accounting nuclear condensation and flow cytometry. When the cells were treated with ATRA at or higher than 1 μM for more than 24 h, significant amount of the apoptotic cells was observed. Induction of apoptosis of Ana-1 cells by ATRA was in time- and dose-dependent manners, exhibiting the similar pattern as the apoptosis induced by actinomycin D (ACTD). ATRA treatment of Ana-1 cells also caused the changes of the mRNA levels of apoptosis-associated gene bcl-2, as detected by Northern blot analysis. The temporal changes of bcl-2 expression by ATRA was also parallel to that by ACTD. In conclusion,ATRA can induce apoptosis in macrophage cells, which may be helpful in understanding of immunological functions retinoids.展开更多
The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, ...The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs, miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mes- enchymat transition, migration, invasion, and metastasis of various cancer celt entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.展开更多
Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through...Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of IncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that IncRNAs participate in the p53 tumor suppressor regulatory network. In this review, we discuss how IncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated IncRNAs in cancer will provide a better understanding of lncRNA- mediated gene regulation in the p53 pathway. As a result, IncRNAs may prove to be valuable biomarkers for cancer diagnosis or poten- tial targets for cancer therapy.展开更多
Computational analysis is essential for transforming the masses of microarray datainto a mechanistic understanding of cancer. Here we present a method for findinggene functional modules of cancer from microarray data ...Computational analysis is essential for transforming the masses of microarray datainto a mechanistic understanding of cancer. Here we present a method for findinggene functional modules of cancer from microarray data and have applied it tocolon cancer. First, a colon cancer gene network and a normal colon tissue genenetwork were constructed using correlations between the genes. Then the modulesthat tended to have a homogeneous functional composition were identified by split-ting up the network. Analysis of both networks revealed that they are scale-free.Comparison of the gene functional modules for colon cancer and normal tissuesshowed that the modules’ functions changed with their structures.展开更多
To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were ...To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were performed to identify differentially expressed genes(DEGs)between primary prostate cancer and CRPC.After that,we performed functional enrichment analysis including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway.In addition,protein–protein interaction(PPI)analysis was used to search for hub genes.Finally,to validate the significance of these genes,we performed survival analysis.As a result,we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets.Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway.PPI network identified hub genes like cortactin-binding protein 2(CTTNBP2),Rho family guanosine triphosphatase(GTPase)3(RND3),protein tyrosine phosphatase receptor-type R(PTPRR),Jagged1(JAG1),and lumican(LUM).Based on PPI network analysis and functional enrichment analysis,we identified two genes(PTPRR and JAG1)as key genes.Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer.In conclusion,PTPRR and JAG1 are key genes in the CRPC,which may serve as promising biomarkers of diagnosis and prognosis of CRPC.展开更多
文摘最新研究进展揭示，抑癌基因功能的抑制或失活，除了与基因片段的丢失，DNA序列的错位、缺失、重组、变换、点突变等机制相关外，还与DNA序列中CpG岛（CpG island）中胞嘧啶（C）碱基环上发生的甲基化（^mCpG）有极其重要的相关性。RASSF1A基因（RAS association domain family 1 Agene）这一由Dammann等发现并命名的基因，在原发性肝癌中的表达情况则未有报道。
基金Supported by National Key Program on Basic Research, No.2004CB518604
文摘AIM： To investigate the role of transglutaminase 3 （TGM3） gene in human esophageal squamous cell carcinoma （ESCC）, and analyze its relationship with clinicopathological parameters. METHODS： Gene expression of TGM3 in fresh esophageal cancer tissues and their corresponding normal mucosas was detected immunohistochemically（I HC） by means of tissue microarray（TMA）. Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 10.0. RESULTS： Expression rate of TGM3 was reduced to 81.8% in ESCC. Expression of TGM3 was significantly inversely correlated with histological grade of esophageal carcinoma （in grade I, II and III tumors, the reduced expression was 4/7, 57/71, and 20/21, respectively, P 〈 0.05）, whereas it had no obvious correlations with lymph node metastasis and depth of invasion. CONCLUSION： Reduced expression of TGM3 may play an important role in esophageal carcinogenesis.
文摘Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer ceils, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 （PRC2）. In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.
文摘Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere maintenance genes has been confirmed.Cumulative evidence shows that the difference of telomere length and stability among the individual depends on the genetic variants of telomere maintenance genes.Genetic variants in telomere maintenance genes may affect telomere length and stability,thus the increased cancer risk.This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.
文摘Macrophage cells play an important role in the initiation and regulation of the immune response. All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids) affect a large number of biological processes.Recently , retinoids have been shown promise in the therapy and prevention of various cancers. However, many interesting questions related to the activities of retinoids remain to be answered: (Ⅰ) Molecular mechanisms by which retinoids exert their effects; (Ⅱ) why the clinical uses of retinoids give undesirable side effects of varying severity with a higher freqllency of blood system symptoms; (Ⅲ)little is known for its impacts on macrophage cells etc. We set up this experiment, therefore, to examine the apoptosis of ATRA on macrophage Ana-1 cell line. Apoptosis of the cells was quantitated, after staining cells with propidium iodide (PI), by both accounting nuclear condensation and flow cytometry. When the cells were treated with ATRA at or higher than 1 μM for more than 24 h, significant amount of the apoptotic cells was observed. Induction of apoptosis of Ana-1 cells by ATRA was in time- and dose-dependent manners, exhibiting the similar pattern as the apoptosis induced by actinomycin D (ACTD). ATRA treatment of Ana-1 cells also caused the changes of the mRNA levels of apoptosis-associated gene bcl-2, as detected by Northern blot analysis. The temporal changes of bcl-2 expression by ATRA was also parallel to that by ACTD. In conclusion,ATRA can induce apoptosis in macrophage cells, which may be helpful in understanding of immunological functions retinoids.
文摘The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs （miRNAs） are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling. Several independent studies identified the members of the miR-34 family as the most prevalent p53-induced miRNAs, miR-34s are frequently silenced in variety of tumor entities, suggesting that they are important tumor suppressors. Indeed, ectopic expression of miR-34s inhibits proliferation, epithelial to mes- enchymat transition, migration, invasion, and metastasis of various cancer celt entities. Moreover, delivery or re-expression of miR-34 leads to notable repression of tumor growth and metastasis in cancer mouse models, and may therefore represent an efficient strategy for future cancer therapeutics. Besides their crucial functions in cancer, members of the miR-34 family also play important roles in spermatogenesis, stem cell differentiation, neuronal development, aging, and cardiovascular functions. Consequently, miR-34 has also been implicated in various non-cancerous diseases, such as brain disorders, osteoporosis, and cardiovascular complications.
文摘Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of IncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that IncRNAs participate in the p53 tumor suppressor regulatory network. In this review, we discuss how IncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated IncRNAs in cancer will provide a better understanding of lncRNA- mediated gene regulation in the p53 pathway. As a result, IncRNAs may prove to be valuable biomarkers for cancer diagnosis or poten- tial targets for cancer therapy.
基金the National Natural Science Foundation of China （Grant No. 60234020）.
文摘Computational analysis is essential for transforming the masses of microarray datainto a mechanistic understanding of cancer. Here we present a method for findinggene functional modules of cancer from microarray data and have applied it tocolon cancer. First, a colon cancer gene network and a normal colon tissue genenetwork were constructed using correlations between the genes. Then the modulesthat tended to have a homogeneous functional composition were identified by split-ting up the network. Analysis of both networks revealed that they are scale-free.Comparison of the gene functional modules for colon cancer and normal tissuesshowed that the modules’ functions changed with their structures.
文摘To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were performed to identify differentially expressed genes(DEGs)between primary prostate cancer and CRPC.After that,we performed functional enrichment analysis including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway.In addition,protein–protein interaction(PPI)analysis was used to search for hub genes.Finally,to validate the significance of these genes,we performed survival analysis.As a result,we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets.Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway.PPI network identified hub genes like cortactin-binding protein 2(CTTNBP2),Rho family guanosine triphosphatase(GTPase)3(RND3),protein tyrosine phosphatase receptor-type R(PTPRR),Jagged1(JAG1),and lumican(LUM).Based on PPI network analysis and functional enrichment analysis,we identified two genes(PTPRR and JAG1)as key genes.Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer.In conclusion,PTPRR and JAG1 are key genes in the CRPC,which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
