Transcriptome Analyses Reveal Adult Metabolic Syndrome With Intrauterine Growth Restriction in Pig Models

Epidemiological data have indicated that intrauterine growth retardation (IUGR) is a risk factor for the adult metabolic syndrome in pigs. However, the causative genetic mechanism leading to the phenotype in adulthood has not been well characterized. In the present study, both normal and IUGR adult pigs were used as models to survey the differences in global gene expression in livers through transcriptome sequencing. The transcriptome libraries generated 104.54 gb of data. In normal and IUGR pigs, 16,948 and 17,078 genes were expressed, respectively. A total of 1,322 differentially expressed genes (DEGs) were identified. Enrichment analysis of the DEGs revealed that the top overrepresented gene ontology (GO) terms and pathways were related to oxidoreductase activity, ATPase activity, amino catabolic process, glucose metabolism, and insulin signaling pathway. The increased gluconeogenesis (GNG) and decreased glycogen synthesis in the liver contributed to the glucose intolerance observed in IUGR. The reduced expression of insulin signaling genes (such as PI3K and AKT) indicated an elevated risk of diabetes in adulthood. Together, these findings provide a comprehensive understanding of the molecular mechanisms of adult IUGR pigs and valuable information for future studies of therapeutic intervention in IUGR metabolic syndrome

The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

Background/Aims: Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Methods: Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. Results: In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Conclusion: Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome

Construction and validation of a prognostic model for hepatocellular carcinoma: Inflammatory ferroptosis and mitochondrial metabolism indicate a poor prognosis

BackgroundAn increasing number of innovations have been discovered for treating hepatocellular carcinoma (HCC or commonly called HCC) therapy, Ferroptosis and mitochondrial metabolism are essential mechanisms of cell death. These pathways may act as functional molecular biomarkers that could have important clinical significance for determining individual differences and the prognosis of HCC. The aim of this study was to construct a stable and reliable comprehensive model of genetic features and clinical factors associated with HCC prognosis.MethodsIn this study, we used RNA-sequencing (fragments per kilobase of exon model per million reads mapped value) data from the Cancer Genome Atlas (TCGA) database to establish a prognostic model. We enrolled 104 patients for further validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses (KEGG) analysis were used for the functional study of differentially expressed genes. Pan-cancer analysis was performed to evaluate the function of the Differentially Expressed Genes (DEGs). Thirteen genes were identified by univariate and least absolute contraction and selection operation (LASSO) Cox regression analysis. The prognostic model was visualized using a nomogram.ResultsWe found that eight genes, namely EZH2, GRPEL2, PIGU, PPM1G, SF3B4, TUBG1, TXNRD1 and NDRG1, were hub genes for HCC and differentially expressed in most types of cancer. EZH2, GRPEL2 and NDRG1 may indicate a poor prognosis of HCC as verified by tissue samples. Furthermore, a gene set variation analysis algorithm was created to analyze the relationship between these eight genes and oxidative phosphorylation, mitophagy, and FeS-containing proteins, and it showed that ferroptosis might affect inflammatory-related pathways in HCC.ConclusionEZH2, GRPEL2, NDRG1, and the clinical factor of tumor size, were included in a nomogram for visualizing a prognostic model of HCC. This nomogram based on a functional study and verification by clinical samples, shows a reliable performance of patients with HCC

TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma

Background/Aim: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC) may fail due to metastasis, in which epithelial-mesenchymal transition (EMT) plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT. Methods: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell). Results: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells. Conclusion: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC

Additional file 1 of Insights into the genetic variability and evolutionary dynamics of tomato spotted wilt orthotospovirus in China

Supplementary Material 1: Figure S1. Representative 1.5% agarose gel showing expected amplicons of all three genomic RNAs of YNHH isolate of TSWV. Figure S2. Recombination Analysis Tool (RAT) output for L segment of TSWV: (A) KP008132 (pepper-Spain), (B) MK348942 (pepper-Italy). Figure S3. Recombination Analysis Tool (RAT) output for M segment of newly reported YNKM-2 isolate of TSWV. Figure S4. Recombination Analysis Tool (RAT) output for S segment of TSWV: (A) MG989674 (pepper-Italy), (B) MG989675 (pepper-Italy). Figure S5. Graphical representation of potential reassortment breakpoints detected among mixed TSWV genomic segments: L, M, and S RNA