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1.
BMC Cancer ; 24(1): 1130, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261761

RESUMEN

Gastric cancer is one of the most malignant digestive tract tumors worldwide and its progression is associated with gene expression and metabolic alteration. We revealed that the gastric cancer patients with lower expression level of TOB1 exhibited poorer overall survivals according to the data in Kaplan-Meier Plotter. The unphosphorylated TOB1 protein which is effective expressed lower in gastric cancer cells. The gastric cancer cells with TOB1 gene depletion performed higher abilities of proliferation, migration and invasion and lower ability of apoptosis in vitro. The TOB1 gene depletion also promoted the tumorigenesis of gastric cancer cells in vivo. The gastric cancer cells with TOB1 gene overexpression had the converse behaviors. The transcriptional and metabolic sequencing was performed. The analyzation results showed that genes correlate-expressed with TOB1 gene were enriched in the pathways related to ERK pathway, including focal adhesion pathway, which was verified using real-time quantitative PCR. After inhibiting ERK pathway, the proliferation, colony formation and migration abilities were reduced in gastric cancer cells with low phosphorylated TOB1 protein expression level. Moreover, Pearson correlation analysis was adopted to further analyze the correlation of enriched metabolic products and differentially expressed genes. The expression of Choline, UDP-N-acetylglucosamine, Adenosine and GMP were related to the function of TOB1. This study demonstrates the genes and metabolites related to focal adhesion pathway and ERK pathway are the potential diagnosis and therapeutic targets to gastric cancer with TOB1 depletion.


Asunto(s)
Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Sistema de Señalización de MAP Quinasas , Neoplasias Gástricas , Proteínas Supresoras de Tumor , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Movimiento Celular/genética , Línea Celular Tumoral , Animales , Ratones , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Adhesiones Focales/genética , Adhesiones Focales/metabolismo , Apoptosis/genética
2.
Front Genet ; 13: 919063, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35801081

RESUMEN

Mitochondrial DNA (mtDNA) has the characteristics of maternal inheritance, high mutation rate, high copy number, and no recombination. As the most powerful tool for studying the origin and evolution of modern humans, mtDNA has great significance in the research of population genetics and evolutionary genetics. Here, we provide new insights into the maternal genetic history of the Daur ethnic group by generating complete mitochondrial genomes from a total of 146 Daur individuals in China. We also collected the published complete mitochondrial genome sequences of 5,094 individuals from 56 worldwide populations as reference data to further explore the matrilineal genetic landscape of the Daur ethnic group. First, the haplotype diversity was 0.9943 ± 0.0019 and nucleotide diversity was 0.0428 ± 0.0210. The neutrality tests of the Daur group showed significant negative values and the mismatch distribution curve was obviously distributed in a unimodal pattern. The results showed that the Daur ethnic group has high genetic diversity and may have experienced recent population expansion. In addition, the main haplogroups of the Daur population were haplogroup D (31.51%), M* (20.55%), C (10.28%), F (7.53%), and B (6.85%), all of which were prevalent in northern China. It probably implies the northern Chinese origin of the Daur population. The PCA, F ST, and phylogenetic analysis results indicated that the Daur group formed a cluster with East Asian populations, and had few genetic differences with the populations in northern China. More importantly, we found that disease-related mutation sites of the mitochondrial genome may be related to ethnic groups, which may have important implications for the prevention and occurrence of specific diseases. Overall, this study revealed the complexity and diversity of the matrilineal genetic background of the Daur ethnic group. Meanwhile, it provided meaningful data for the research on the diversity of the human genome.

3.
Pharmgenomics Pers Med ; 14: 1537-1547, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34876832

RESUMEN

INTRODUCTION: Genetic variability in genes encoding drug-metabolizing enzymes may contribute to the heterogeneity of drug responses in different populations. Extensive research in pharmacogenomics in major populations around the world provides us with a great deal of information about drug-related genetic polymorphisms. OBJECTIVE: The purpose of this study was to detect the genetic variation of drug-metabolism-related genes in the five ethnic minorities Daur, Hezhen, Ewenki, Mongolian and Manchu in China, and to analyze the distribution differences among ethnic groups. METHODS: We genotyped 32 SNPs of drug metabolism genes in 882 healthy Chinese volunteers from five ethnic groups. The genotype frequency and allele frequency of the five ethnic groups were calculated, and the different variants among the five ethnic groups were compared by chi-square test. Genetic parameters were analyzed using Popgene software. The genetic structure of five ethnic minorities was analyzed by principal component analysis, and compared with 26 populations. RESULTS: We found that SNPs of genes related to drug metabolism existed diversity in different populations. Among them, rs8192766 and rs9419082 in CYP2E1 showed statistical differences between Daur and Manchu, and NAT2 rs1801280 showed statistical differences between Hezhen and Mongolian. In addition, the five populations we studied had the smallest differences with EAS populations. There was haplotype diversity in CHST3, VKORC1, CYP1A2 and CYP2E1 genes in the five ethnic minorities, and these haplotype polymorphisms were related to the use of corresponding drug doses. Cluster analysis shows that the five ethnic minorities in Heilongjiang Province are clustered together with the EAS populations. CONCLUSION: These results suggest that understanding the diversity of drug-related genetic markers is critical for individualized drug gene therapy programs in ethnic minorities in China as well as in populations highly mixed with these ethnic groups.

4.
Front Genet ; 12: 756802, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745225

RESUMEN

Musculoskeletal performance is a complex trait influenced by environmental and genetic factors, and it has different manifestations in different populations. Heilongjiang province, located in northern China, is a multi-ethnic region with human cultures dating back to the Paleolithic Age. The Daur, Hezhen, Ewenki, Mongolian and Manchu ethnic groups in Heilongjiang province may have strong physical fitness to a certain extent. Based on the genetic characteristics of significant correlation between some important genes and skeletal muscle function, this study selected 23 SNPs of skeletal muscle strength-related genes and analyzed the distribution of these loci and genetic diversity in the five ethnic groups. Use Haploview (version 4.1) software to calculate the chi-square and the Hardy-Weinberg equilibrium to assess the difference between the two ethnic groups. Use R (version 4.0.2) software to perform principal component analysis of different ethnic groups. Use MEGA (version 7.0) software to construct the phylogenetic tree of different ethnic groups. Use POPGENE (version 1.32) software to calculate the heterozygosity and the FST values of 23 SNPs. Use Arlequin (version 3.5.2.2) software to analyze molecular variance (AMOVA) among 31 populations. The results showed that there was haplotype diversity of VDR, angiotensin-converting enzyme, ACTN3, EPO and IGF1 genes in the five ethnic groups, and there were genetic differences in the distribution of these genes in the five ethnic groups. Among them, the average gene heterozygosity (AVE_HET) of the 23 SNPs in the five populations was 0.398. The FST values of the 23 SNPs among the five ethnic groups varied from 0.0011 to 0.0137. According to the principal component analysis, the genetic distance of Daur, Mongolian and Ewenki is relatively close. According to the phylogenetic tree, the five ethnic groups are clustered together with the Asian population. These data will enrich existing genetic information of ethnic minorities.

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