Energy metabolism heterogeneity is a hallmark in ovarian cancer; namely, the Warburg and reverse Warburg effects coexist in ovarian cancer. Exploration of energy metabolism heterogeneity benefits the discovery of the effective biomarkers for ovarian cancers. The integrative analysis of transcriptomics (20,115 genes in 419 ovarian cancer samples), proteomics (205 differentially expressed proteins), and mitochondrial proteomics (1198 mitochondrial differentially expressed proteins) revealed (i) the upregulations of rate-limiting enzymes PKM2 in glycolysis, IDH2 in Krebs cycle, and UQCRH in oxidative phosphorylation (OXPHOS) pathways, (ii) the upregulation of PDHB that converts pyruvate from glycolysis into acetyl-CoA in Krebs cycle, and (iii) that miRNA (hsa-miR-186-5p) and RNA-binding protein (EIF4AIII) had target sites in those key proteins in energy metabolism pathways. Furthermore, lncRNA SNHG3 interacted with miRNA (hsa-miR-186-5p) and RNA-binding protein (EIF4AIII). Those results were confirmed in the ovarian cancer cell model and tissues. It clearly concluded that lncRNA SNHG3 regulates energy metabolism through miRNA (hsa-miR-186-5p) and RNA-binding protein (EIF4AIII) to regulate the key proteins in the energy metabolism pathways. SNHG3 inhibitor might interfere with the energy metabolism to treat ovarian cancers. These findings provide more accurate understanding of molecular mechanisms of ovarian cancers and discovery of effective energy-metabolism-heterogeneity therapeutic drug for ovarian cancers.
Part of the book: Molecular Medicine
The invasive characteristic of nonfunctional pituitary adenoma (NFPA) is an important clinical problem without a clear molecular mechanism, which severely challenges its treatment strategy. Clarification of the proteomic alterations between invasive and non-invasive NFPAs is the key step for in-depth understanding of its mechanisms and discovering reliably invasive biomarkers. Two-dimensional gel electrophoresis (2DGE)-based comparative proteomics was carried out between four invasive and four non-invasive NFPAs. A total of 64 upregulated protein-spots and 39 downregulated protein-spots were identified among 24 (invasive n = 12; non-invasive n = 12) 2DGE maps (ca. 1200 spots/gel). Mass spectrometry identified 30 upregulated proteins and 27 downregulated proteins between invasive and non-invasive NFPAs. Those 57 differentially expressed proteins are involved in multiple biological functions, including oxidative stress, mitochondrial dysfunction, MAPK signaling alteration, proteolysis abnormality, CDK-C signaling, amyloid processing, and TR/RXR activation. These findings provide important clues to insights into molecular mechanisms of invasive NFPAs and to discovery of effective biomarkers for effective treatment of invasive NFPA patients.
Part of the book: Proteomics Technologies and Applications