Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cluster nuclearity control and modulated hydrothermal synthesis of functionalized Zr-12 metal-organic frameworks

10.1039/c8dt05060kDALTON TRANSACTIONS48217069-707

Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Abstract Background The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. Methods In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. Results The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08–2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32–4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39–4.50; p = 0.002) in patients with breast cancer. Conclusion Our findings revealed that a IDH1low/Snailhigh molecular signature could serve as an independent biomarker for poor prognosis in breast cance

Additional file 7: of Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Figure S3. IDH1 stable knockdown significantly promoted MDA-MB-231 cell motility. (a) The expression levels of IDH1 were examined in two IDH1 stable knockdown MDA-MB-231 cells (shIDH1#1 and shIDH1#2) through western blotting. (b) Invasion ability was assessed using the Transwell assay in MDA-MB-231 cells with IDH1 stable knockdown and a scrambled control. The cell images of the representative experiment are provided. (c) Values were quantified using Ascent software, as detailed. Data are reported as the number of invading cells relative to the control (means Âą standard deviation (SD)). (d) Expression levels of IDH1, snail, slug, twist, and actin were examined in shIDH1#1, shIDH1#2, and the scrambled control through western blotting. (TIFF 3572 kb

Additional file 1: of Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Table S1. Primer sequence list. (DOC 38 kb

Additional file 8: of Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Figure S4. IDH1 knockdown significantly accelerated HS578T and BT549 cell motility. (a), (d) Invasion ability was assessed using the Transwell assay in HS578T and BT549 cells with si-IDH1 and scramble control. The cell images of a representative experiment are shown. (b), (e) Values quantified using Ascent software are shown. Data are reported as the number of colonies relative to the control (means Âą standard deviation (SD)). (c), (f) Expression levels of EMT-related markers were examined in HS578T and BT549 cells transfected with si-IDH1 and scramble control by western blotting. (TIFF 4403 kb

Additional file 3: of Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Table S3. Correlation of IDH1 expression with molecular markers in patients with breast cancer. (DOCX 16 kb

Additional file 9: of Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Figure S5. IDH1 knockdown accelerated MCF7 cell proliferation and migration ability. (a) the expression levels of IDH1 were examined in MCF7 cells with siIDH1#1, siIDH1#2, and control transfection through western blotting. (b) A wound healing assay was employed to examine MCF7 cells transfected with siIDH1#1, siIDH1#2, and the scrambled control. (c) The expression levels of IDH1, snail, slug, twist and actin were examined in siIDH1#1, siIDH1#2, and the scrambled control through western blotting. (d) The proliferation assay was performed in MCF-7 cells transfected with the scrambled control, siIDH1#1 and siIDH1#2, respectively. (TIFF 4527 kb

Additional file 10: of Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability

Figure S6. Gene set enrichment analysis for differential expression of genes in MDA-MB-231 cells transfected with si-IDH1 compared with those transfected with scramble control. (a) Differential expression of genes (upregulated or downregulated twofold change) was identified using a microarray approach. These gene sets were significantly enriched in metastasis-associated terms from the Kyoto Encyclopedia of Genes and Genomes. (b) Schematic putative signaling pathway illustrating IDH1-modulated cancer cell invasion. (TIFF 1728 kb