Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysregulated microRNA (miRNA) mediate malignant phenotypes, including metabolic reprogramming. By performing an integrative analysis of miRNA and metabolome data for the NCI-60 cell line panel, we identified an miRNA cluster strongly associated with both c-Myc expression and global metabolic variation. Within this cluster the cancer-associated and cardioprotective miR-22 was shown to repress fatty acid synthesis and elongation in tumour cells by targeting ATP citrate lyase and fatty acid elongase 6, as well as impairing mitochondrial one-carbon metabolism by suppression of methylene tetrahydrofolate dehydrogenase/cyclohydrolase. Across several data sets, expression of these target genes were associated with poorer outcomes in breast cancer patients. Importantly, a beneficial effect of miR-22 on clinical outcomes in breast cancer was shown to depend on the expression levels of the identified target genes, demonstrating the relevance of miRNA/mRNA interactions to disease progression in vivo. Our systematic analysis establishes miR-22 as a novel regulator of tumour cell metabolism, a function that could contribute to the role of this miRNA in cellular differentiation and cancer development. Moreover, we provide a paradigmatic example of effect modification in outcome analysis as a consequence of miRNA-directed gene targeting, a phenomenon that could be exploited to improve patient prognosis and treatment.
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PMID:Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells. 2647 10

The fatty acid compositions of the fish muscle and liver are substantially affected by rearing environment. However, the mechanisms underlying this effect have not been thoroughly described. In this study, we investigated the effects of different culture patterns, i.e., marine cage culture and freshwater pond culture, on long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis in an aquaculturally important fish, the Japanese sea bass (Lateolabrax japonicus). Fish were obtained from two commercial farms in the Guangdong province, one of which raises Japanese sea bass in freshwater, while the other cultures sea bass in marine cages. Fish were fed the same commercial diet. We found that omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) levels in the livers and muscles of the marine cage cultured fish were significantly higher than those in the livers and muscles of the freshwater pond cultured fish. Quantitative real-time PCRs indicated that fatty acid desaturase 2 (FADS2) transcript abundance was significantly lower in the livers of the marine cage reared fish as compared to the freshwater pond reared fish, but that fatty acid elongase 5 (Elovl5) transcript abundance was significantly higher. Consistent with this, two of the 28 CpG loci in the FADS2 promoter region were heavily methylated in the marine cage cultured fish, but were only slightly methylated in freshwater pond cultured fish (n = 5 per group). Although the Elovl5 promoter was less methylated in the marine cage reared fish as compared to the freshwater pond reared fish, this difference was not significant. Thus, our results might indicate that Elovl5, not FADS2, plays an important role in the enhancing LC-PUFA synthesis in marine cage cultures.
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PMID:Seawater Culture Increases Omega-3 Long-Chain Polyunsaturated Fatty Acids (N-3 LC-PUFA) Levels in Japanese Sea Bass (Lateolabrax japonicus), Probably by Upregulating Elovl5. 3295 27