Spermine Synthase and MYC Cooperate to Maintain Colorectal Cancer Cell Survival by Repressing Bim Expression

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis and causes tumor regression, but these effects are profoundly attenuated by silencing Bim. These findings uncover a key survival signal in CRC through convergent repression of Bim expression by distinct SMS- and MYC-mediated signaling pathways. Thus, combined inhibition of SMS and MYC signaling may be an effective therapy for CRC

The complete chloroplast genome of cultivated apple (Malus domestica Cv. ‘Yantai Fuji 8’)

The cultivated apple (Malus domestica Borkh.) is one of the most important crop fruits with high-economic values in the world. In the present study, we characterized the complete chloroplast (cp) genome sequence of apple cultivar ‘Yantai Fuji 8’. The complete cp genome is 160,062 bp in length with a typical quadripartite structure. A total of 112 unique genes were found in the newly sequenced genome, including 78 protein-coding, 30 tRNA, and 4 rRNA genes. Of these, 7 protein-coding genes, 7 tRNA genes, and all 4 rRNA genes are duplicated in the inverted regions. A maximum likelihood phylogenetic tree was reconstructed using the full length of cp genome to show the relationships among species in Rosaceae. The complete cp genome will be potential genetic resources for apple breeding programs

The mitochondrial genome of Ectropis dentilineata Moore, 1868 (Lepidoptera: Geometridae) from tea plantations in Guizhou province, China

Ectropis dentilineata Moore, 1868 has a wide geographic distribution while its genome data are largely unknown. In this study, we collected samples of E. dentilineata from a tea plantation in Guizhou province, China. Illumina sequencing showed that the mitochondrial genome of E. dentilineata is 15,356 bp in length, containing the entire set of 37 mitochondrial genes. Several tRNAs show gene arrangements compared with the ancestral gene order, mainly involving the tRNA cluster (M-I-Q). These data will facilitate a deeper understanding and exploitation of E. dentilineata

A plasma proteomic approach in patients with heart failure after acute myocardial infarction: insights into the pathogenesis and progression of the disease

AimsThe pathogenesis of disease progression targets for patients with heart failure after acute myocardial infarction was investigated by using plasma proteomics.MethodsThe plasma proteomes of acute myocardial infarction patients with (MI-HF) and without (MI-WHF) heart failure were compared. Each group consisted of 10 patients who were matched for age and sex. The peptides were analyzed by 2-dimensional liquid chromatography coupled to tandem mass spectrometry in a high definition mode. Parallel reaction monitoring (PRM) verified the selected target proteins.ResultsWe identified and quantified 2,589 and 2,222 proteins, respectively, and found 117 differentially expressed proteins (DEPs) (≥1.5-fold), when the MI-HF and MI-WHF groups were compared. Of these 51 and 66 were significantly up-regulated and down-regulated, respectively. The significant DEPs was subjected to protein–protein interaction network analysis which revealed a central role of the NF-κB signaling pathway in the MI-HF patients. PRM verified that MB, DIAPH1, VNN1, GOT2, SLC4A1, CRP, CKM, SOD3, F7, DLD, PGAM2, GOT1, UBA7 and HYOU1 were 14 proteins which were highly expressed in MI-HF patients.ConclusionsThese findings showed a group of proteins related to the NF-κB signaling pathway in the pathogenesis of patients with poor outcomes after experiencing MI-HF. These proteins may be useful candidate markers for the diagnosis of MI-HF as well as help to elucidate the pathophysiology of this major cause of mortality in older patients

The Effects of Different Levels of Dietary Protein and L-Carnitine on Blood Sugar and Lipids of the New GIFT Strain of Juvenile Nile Tilapia (Oreochromis niloticus)

The new GIFT (Genetically Improved Farmed Tilapia) strain of Nile tilapia is a popular cultivated fish in Asia, but intensive aquaculture using nutritionally imbalanced feed has led to disorder of lipid metabolisms. An 8-week feeding experiment was conducted in order to assess the effects of different levels of L-carnitine (0, 200, 400, 600, and 800 mg/kg) and dietary protein (22, 25, and 28%) on blood sugar and blood lipid contents of the new juvenile GIFT strain of Nile tilapia. Results showed that dietary protein and L-carnitine had significant influences on glucose (GLU), high-density lipoprotein–cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein–cholesterol (LDL-C) in the blood serum. The contents of GLU and HDL-C increased with the increases in dietary protein and L-carnitine levels, while the contents of TC, LDL-C, and TG decreased with the increases in dietary protein and L-carnitine levels. The interactive effect of both dietary protein and L-carnitine was most significant on GLU (p = 0.0001), followed by TG (p = 0.001), TC (p = 0.005), HDL-C (p = 0.056), and LDL-C (p = 0.109). These results suggested that high levels of dietary protein and L-carnitine supplementation reduce blood lipids and the burden of the fish liver

Chromosome 8 gain is associated with high-grade transformation in MPNST

One of the most common malignancies affecting adults with Neurofibromatosis type 1 (NF1) is the malignant peripheral nerve sheath tumor (MPNST), an aggressive and often fatal sarcoma that commonly arises from benign plexiform neurofibromas. Despite advances in our understanding of MPNST pathobiology, there are few effective therapeutic options, and no investigational agents have proven successful in clinical trials. To further understand the genomic heterogeneity of MPNST, and to generate a preclinical platform that encompasses this heterogeneity, we developed a collection of NF1-MPNST patient-derived xenografts (PDX). These PDX were compared with the primary tumors from which they were derived using copy number analysis, whole exome sequencing, and RNA sequencing. We identified chromosome 8 gain as a recurrent genomic event in MPNST and validated its occurrence by FISH in the PDX and parental tumors, in a validation cohort, and by single-cell sequencing in the PDX. Finally, we show that chromosome 8 gain is associated with inferior overall survival in soft-tissue sarcomas. These data suggest that chromosome 8 gain is a critical event in MPNST pathogenesis and may account for the aggressive nature and poor outcomes in this sarcoma subtype

Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression

Polyamine metabolism is frequently dysregulated in cancers. Here, the authors show that a polyamine biosynthetic enzyme, spermine synthase, is overexpressed in colorectal cancers and cooperates with MYC to prevent cancer cell apoptosis by repression of proapoptotic protein, Bim

Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy

Objective. Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods. Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results. 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree=24), GNB3 (degree=23), QSOX1 (degree=21), and APOB (degree=17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion. Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM