The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis. Since functional variations in these two genes were shown to change gene expression and function, we hypothesized that potentially functional polymorphisms in these genes may contribute to colorectal cancer (CRC) susceptibility. A hospital-based case-control study consisting of 444 patients and 569 controls was conducted to explore the associations between TP53 Arg72Pro and MDM2 T309G and CRC risk in Chinese. The combined effect of TP53 Arg72Pro and MDM2 T309G was significant in a gene dose-response increasing CRC risk (trend test: P = 0.02). Individuals carrying 3 or more potential risk alleles had 1.78 times risk (95 % CI: 1.13-2.80) to develop CRC compared with individuals without potential risk allele. This increased cancer risk was more pronounced in smokers who carried 3-4 potential risk alleles (OR = 2.75, 95 % CI: 1.14-6.60) and in young subjects (OR = 2.05, 95 % CI: 1.08-3.88). The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of CRC in Chinese, especially in smokers, and this kind of interaction is associated with onset age of CRC.
Hypoxia is a typical microenvironment feature in almost all solid tumors and is frequently associated with growth of cancers including colorectal cancer (CRC). This study focuses on the influence of hypoxic microenvironment on the activity of CRC cells and the molecules involved. CRC cells were cultured under hypoxic conditions for 48 h, after which the proliferation, migration, invasion, and epithelial-mesenchymal transition activities of cells were increased. MicroRNA- (miR-) 19a was significantly upregulated in cells after hypoxia exposure according to a microarray analysis. STAT3 was confirmed as an upstream regulator of miR-19a which bound to the promoter region of miR-19a at the 96 bp/78 bp sites, and miR-19a bound to the PTEN mRNA to activate the PI3K/AKT signaling pathway. Hypoxia exposure induced STAT3 phosphorylation and PTEN knockdown in CRC cells. Silencing of STAT3 reduced the hypoxia-induced activity of CRC cells, whereas the malignant behaviors of cells were restored after miR-19a upregulation but blocked after PTEN overexpression. Similar results were reproduced in vivo where downregulation of STAT3 or overexpression of PTEN suppressed tumor growth and metastasis in nude mice. This study demonstrated that hypoxia augments activity and malignant behaviors of colorectal cancer cells through the STAT3/miR-19a/PTEN/PI3K/AKT axis.
A total of 10 non-repetitive multi-drug-resistant Acinetobacter strains were collected. With reference to A . c a l c o a c e t i c u s ( A T C C 2 3 0 5 5 ) , A . b a u m a n n i i (ATCC19606), A. lwoffii (ATCC17986), and A. junii (NCTC5866), DNA fingerprint technique, amplified ribosomal DNA restriction analysis (ARDRA), and random amplified polymorphism DNA (RAPD) were carried out to identify the genomic species of Acinetobacter spp. The distances between them were calculated by the unweighted pair group method with arithmetic (UPGMA). Genotypes of Acinetobacter spp. were effectively classified and an A. junii together with nine A. baumannii isolates was genomically identified. The combination of ARDRA and RAPD DNA-fingerprint technique shows high complementarity, and could be a useful tool in Acinetobacter genomic species identification.
The Gastrodia tuber, as well as the gastrodine extract derived from it, has been found to have many pharmacological effects. The gastrodine content of different tuber populations was determined, and their genomic DNA fingerprints were investigated. Through recovery, cloning, sequencing and bioinformatics analyses of DNA fragments, five DNA sequences were proved to be new discoveries. Using the PCR technique, we further studied the distribution of the sequences in eight Gastrodia populations, as well as their correlation with gastrodine content. The distribution of the five DNA sequences varied greatly among the populations. DNA sequences 1 and 5 were found in all the populations studied and determined to be specific DNA molecular markers that differentiate Gastrodia from other species. DNA sequence 2 was found only in the populations showing the highest gastrodine content. Hence, these sequences can be applied to identify genuine Gastrodia tubers and to optimise the selection of better populations.
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