Yap1 Hydroxylation Suppress Prostate Cancer Metastasis

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The overexpression of MRP4 is related to multidrug resistance in osteosarcoma cells

Doxorubicin (Adriamycin, ADM) is an antimitotic drug used in the treatment of a wide range of malignant tumors, including acute leukemia, lymphoma, osteosarcoma, breast cancer, and lung cancer. Multidrug resistance-associated proteins (MRPs) are members of a superfamily of ATP-binding cassette (ABC) transporters, which can transport various molecules across extra- and intra-cellular membranes. The aim of this study was to investigate whether there was a correlation between MRP4 and primary ADM resistance in osteosarcoma cells. In this paper, we chose the human osteosarcoma cell line MG63, ADM resistant cell line MG63/DOX, and the patient′s primary cell GSF-0686. We checked the ADM sensitivity and cytotoxicity of all the three cells by cell proliferation assay. The intracellular drug concentrations were measured by using LC-MS/MS. We also examined MRP4 gene expression by RT-PCR and Western Blot. We found that the intracellular ADM concentration of the parent osteosarcoma cell line MG63 was higher than the ADM resistant osteosarcoma MG63/DOX cell line or the GSF-0686 cell after ADM treatment (P < 0.05). In addition, MRP4 mRNA and protein levels in ADM resistant osteosarcoma cells were higher than in MG63 cell (P < 0.05). Taking together, this work suggests that overexpression of MRP4 may confer ADM resistance in osteosarcoma cells

Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma

Purpose: To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients. Methods: Fluorescent quantitative real-time PCR was applied to study the mRNA levels of Ezrin, CD44 and Six1 genes in 32 osteosarcoma patient samples and 10 adjacent normal tissues and MG63 osteosarcoma cell lines. The analysis of relationships between pulmonary metastasis and overall survival time were carried out based on the clinical data. Results: mRNA levels of Ezrin and Six1 genes in osteosarcoma tissues were higher than those in adjacent normal tissues (P=0.015, 0.025). The mRNA levels of Ezrin, CD44 and Six1 genes were closely correlated with Enneking GTM clinical staging, while no correlations were demonstrated between the mRNA level of these genes with sex, age, location or pathological types. In addition, we demonstrated that the high mRNA level of Ezrin gene was related to shorter lung metastasis-free and overall survival time of the Chinese patients with osteosarcoma (P < 0.001). Conclusion: Our data suggest that Ezrin, but not CD44 and Six1, could be a prognostic factor and a predictor of potential lung metastasis in osteosarcoma. Further large sample studies need to be done to confirm the potential value of Ezrin as a new therapeutic target

Common Variants in Promoter of ADTRP Associate with Early-Onset Coronary Artery Disease in a Southern Han Chinese Population.

The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD

Analysis of genotypic association of eight SNPs with CAD.

<p><i>P</i>_obs, observed <i>P</i> value; <i>P</i>_adj, <i>P</i> value after adjusted for covariates of gender, age, hypertension, diabetes, blood lipid profiles, smoking; OR_adj, odds ratio after adjustment for the covariates; CI, confidence interval.</p><p>Analysis of genotypic association of eight SNPs with CAD.</p

Overview of LD structure among eight SNPs.

<p>A was constructed based on the genotype data of all the subjects in this work, B was constructed based on the genotype data of subjects excluding late-onset CAD patients. D’ was signed with a number in a diamond. Red diamond without a number refers to D’ = 100. F refers to exon 1, L refers to the last exon. Arrow refers to the transcription direction of <i>ADTRP</i>.</p

Difference of <i>ADTRP</i> mRNA expression between groups with different genotypes of rs7753407, and between early-onset CAD cases and controls.

<p>Levels of <i>ADTRP</i> mRNA expression in leukocytes from 134 randomly selected subjects were measured using real-time qRT-PCR. The average level of it in 61 subjects with the risk genotype AA of rs7753407 was significantly lower than that in 73 subjects with genotype GG or GA (<i>P</i> < 0.01, bars represent mean±S.E.). The average level in 37 early-onset CAD cases was significantly lower than that in 49 controls (<i>P</i> < 0.05, bars represent mean±S.E.).</p