ABSTRACT
Numerous epidemiological studies have studied the association of adiponectin (ADIPOQ) gene and adiponectin receptor (ADIPOR) gene polymorphisms with risk of colorectal cancer (CRC),but the outcomes were incomplete and inconsistent.Therefore,we conducted a meta-analysis to assess the associations systematically.All eligible case-control studies published up to Jan.2015 were searched from PubMed,the Cochrane library,Elsevier,Wiley Online library,China National Knowledge Infrastructure,WanFang data and Chongqing VIP.Effect sizes of odds ratio (OR) and 95％ confidence interval (95％CI) were calculated by using a fixed-or random-effect model.Twelve case-control studies including 6141 cases and 7398 controls were selected.Significant differences in the distributions of allele frequency with CRC risk were directly present in ADIPOQ variants rs2241766,rs1501299 and ADIPOR variant rs1342387.In stratified analysis for different populations,significant differences were present in ADIPOQ variant rs822396 for Ashkenazi Jewish,in ADIPOQ variant rs1501299 and ADIPOR variant rs1342387 for Chinese and in ADIPOQ variant rs 2241766 for Ashkenazi Jewish and Chinese.In addition,the factors correlated with insulin resistance had synergistic effect with ADIPOQ variants rs2241766 T/G and rs1501299 G/T on risk of CRC.ADIPOQ variants rs2241766 T/G,rs1501299 G/T and ADIPOR variant ADIPOR rs1342387 G/A had a population specific correlation with CRC risk,which may be mediated by insulin resistance.And large well-designed studies are still needed for further evaluation of rs822396 and rs1063538,especially for their interaction and combined effect in the correlation with CRC risk.
ABSTRACT
We studied the regulatory effects of the estragen receptorβ(ERβ)gene on the downstream estrogen signal transfection pathway in colon cancer cells and the possible mechanisms involved.A human ERβ gene recombinant expression plasmid,pEGFP-C1-ERβ,was constructed and transfected into the Caco-2 colon cancer cell line,a line with low ERβ gene expression.The expression of ERβmRNA and protein was detected 72 h after transfection.RT-PCR was used to examine the expression levels of the progesterone recepror(PR)gene containing the classic estrogen response element(ERE),the C-fos oncogene containing the AP-1 site(a non-classical ER binding site),the epigenetic modifying genes,such as Dnmt1,Dnmt3a,Dnmt3b,and histone methyltransferase(HMT),and the human mismatch repair gene hMLH1.Methylation-specific PCR was used to detect the changes in the methylated sites of the CpG islands in the promoters of the ERβ,PR,and C-fos genes.The results indicated that the human ERβ gene recombinant expression plasmid pEGFP-C1-ERβ was successfully constructed and transfected into Caco-2 cells.As compared with the control group,the mRNA and protein expression of ERβ gene was increased significantly 72 h after the transfection of pEGFP-C1-ERβ into the Caco-2 cells.As compared with the control group,the mRNA expression of the PR,C-fos,Dnmt3a and Dnmt3b genes was increased significantly 72 h after the transfection of pEGFP-C1-ERβ into the Caco-2 cells,but the mRNA expression of the Dnmt1,HMT,and hMLH1 genes decreased significantly(P<0.05).As compared with the control group,different degrees of demethylation occurred in the promoters of the ERβ,progesterone receptor(PR),and C-fos oncogene 72h after the transfection of pEGFP-C1-ERβ into the Caco-2 cells.The methylation index of the estrogen signal transfection pathway in Caco-2 cells was decreased significantly following the expression restoration of ERβ gene(P<0.05).It is concluded that the restoration or up-regulation of the ERβ gene in Caco-2 cells may significantly activate the expression of the related target genes in the downstream estrogen signal transfection pathway and may result in the demethylation changes of the pathway.During the process,the expression level and activity of the epigenetic modifying genes and the human mismatch repair gene have changed simultaneously.The regulatory effect of the ERβ gene on the estrogen signal transfection pathway to a certain extent partly involves demethylation.
ABSTRACT
This study examined the mRNA expression of NALP3 in the spleen of the mice with hypersplenism due to portal hypertension(PH).The mouse hypersplenism models were established by oral administration of tetrachloromethane(2 mL/kg/week for 12 weeks by oral gavage).All the mice were randomly divided into a control group and an experimental group.The blood routine test was conducted,spleen index was calculated and spleen was histologically examined.Portal vein sera were taken for detection of the level of uric acid.The mRNA expressions of NALP3 and IL-1β in the spleen were detected by reverse transcriptase-polymerase chain reaction(RT-PCR).The results showed that the platelet count was significantly lower in the experimental group[(674±102)× 109/L]than in the control group[(1307± 181)× 109/L](P<0.05),while the spleen index was significantly higher[(9.83±1.36)μg/g]in the experimental group than in the control group[(4.11±0.47)μg/g](P<0.05).The histopathological changes of spleen followed the pattern of congestive splenomegaly.No significant difference was found in the uric acid level in the portal vein between the control group and the experiment group.The mRNA expressions of NALP3 and IL-1β were up-regulated significantly in the spleen in the experimental group as compared with those in the control group(P<0.05).It was concluded that NALP3 and IL-1β may play important roles in the pathogenesis of hypersplenism.
ABSTRACT
This study constructed siRNA recombinant expression vector targeting survivin gene and observe the apoptosis induction effect of it in human colon cancer cells,siRNA recombinant expres-sion vector targeting survivin gene was constructed and transfected into human colon cancer cells.The effect of siRNA recombinant expression vector was detected by RT-PCR,Western blot,MTT re-duction assay and flow cytometry.It was confirmed by restriction endonuclease and sequence analy-sis that siRNA recombinant expression vector targeting survivin gene was constructed successfully.Inhibition rate of survivin siRNA at mRNA and protein levels was 36.33% and 44.65% respectively.Growth of cancer cells was inhibited and the apoptosis rate was (17.24±2.13)%.The siRNA recom-binant expression vector targeting survivin gene has been constructed successfully.It not only can in-hibit the expression of survivin gene,but also can induce apoptosis in human colon cancer cells re-markably.