ABSTRACT
OBJECTIVE@#To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME).@*METHODS@#CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines.@*RESULTS@#The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell.@*CONCLUSION@#FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.
Subject(s)
Humans , Actins , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Chromosomal Proteins, Non-Histone , DNA-Binding Proteins , Drugs, Chinese Herbal/therapeutic use , Lung Neoplasms/metabolism , Tumor MicroenvironmentABSTRACT
Objective To investigate gene polymorphisms and distribution features of glutathione Stransferase Omega-1 (GSTO 1 ) gene in Ala 140Asp site in 16 Chinese populations.MethodsA total of 1369 samples were from the human genome project(HGP)-the establishment and preservation program of Chinese minority genetic resources.The phenotypes of Ala/Ala (C/C),Ala/Asp (C/A),and Asp/Asp (A/A) of GSTO1 Ala140Asp were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).With analysis of molecular variance(AMOVA),the genetic variation levels among nations and regions were analyzed by estimating the evolutionary distance of alleles or genotypes.ResultsOf the 1369 individuals analyzed,979 (71.51％) were carriers of the wild homozygous allele Ala/Ala(C/C),365 (26.66％) were heterozygotes Ala/Asp(C/A) and 25 (1.83％) were mutant homozygotes Asp/Asp(A/A),with an overall frequency of the GSTO 1 mutant allele A 15.16％ [ (365 +50)/( 1369 × 2)].AMOVA analysis showed that the difference was statistically significant(P ＜ 0.05) of genetic variations of GSTO1 gene Ala140Asp among the 14 ethnic groups,and was significant between the northem and southern populations (P ＜ 0.05 ).Conclusion In different regions and populations the GSTO1Ala140Asp mutant allele frequencies are different.
ABSTRACT
Objective To investigate and evaluate the polymorphism distribution of arsenic(+3 oxidation state)methyhransferase(AS3MT)5'-UTR VNTR in Chinese populations.Methods Genomic DNA was extracted from peripheral blood anti-coagulated with ACD of 1440 individuals in a standard phenol-chloroform protocol.The phenotypes of AS3MT 5'-UTR VNTR were determined by polymerase chain reaction(PCR)associated with agarose gel electrophoresis.Results Of the 1440 individuals,771(53.5%),426(29.6%),211(14.7%),16(1.1%)and 16(1.1%)were carriers of the V2/V3(AB/A2B),V3/V3(A2B/A2B),V2/V2(AB/AB),V2/V4(AB/A3B)and V3/V4(A2B/A3B)genotype,respectively.The AB(V2),A2B(V3)and A3B(V4)allele frequency was 41.9%,57.0%,1.1%respectively.The differences of AB(V2)and A2B(V3)allele frequency were all significant between the northern and southern populations respectively(χ2=23.39,χ2=33.28,P＜0.007).Conclusions In different regions the AB(V2)and A2B(V3)allele frequency is different,the AS3MT 5'-UTR VNTR polymorphism can be used to evaluate the susceptivity of arsenieosis.