Differentially expressed lncRNAs and mRNAs in the adipose tissue between cancer associated cachexia mice and normal mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118611 | GEO | 2018/08/16
REPOSITORIES: GEO
Similar Datasets
Project description:Cancer-associated cachexia (CAC) is a wasting syndrome caused by malignant tumors. Fat loss plays a significant role in the pathophysiology of cancer-associated cachexia. The mechanism of fat loss in CAC includes enhancement of lipolysis, inhibition of lipogenesis and browning of white adipose tissue. In order to discover potentially functional genes in white adipose tissue of CAC, we used transcriptome sequencing technology to find research-valuable genes in white adipose tissue (WAT) of CAC rodent model. C57/bl6 mice with LLC tumors were used as the in vivo model for CAC, while normal mice subcutaneously injected with phosphate buffer solution were used as the control group. Overall, our data revealed genes that were differentially expressed in the white adipose tissue of LLC tumor-bearing mice, providing a molecular framework for the investigation into CAC fat loss.
2023-09-15 | GSE242812 | GEO
Project description:Cancer-associated cachexia (CAC) is a metabolic syndrome characterized by progressive depletion of adipose and muscle tissue which cannot be corrected by conventional nutritional therapy. Adipose tissue, as an important energy storage, could appear obvious loss in early stage of CAC, which becomes a negative factor affecting the quality of life, efficacy of chemotherapy and so on. In order to identify differentially expressed RNAs in adipose tissue of CAC patients with noncachexia patients, we chose three gastric cancer patients with remarkable weight loss as CAC group and three gastric cancer patients without significant weight change within half a year as the control group. We resected a small subcutaneous adipose tissue from the abdomen of these six patients at time of surgery and completed transcriptome sequencing using Illumina platform. Compared with NCBI genome detabase, etc, we finally identified 386 differentially expressed mRNAs, 410 differentially expressed lncRNAs, 66 differentially expressed cirRNAs and 98 differentially expressed miRNAs. We hoped to provide more bases for follow-up study of adipose metabolism in cachexia.
2021-05-10 | GSE174128 | GEO
Project description:Cachexia is a wasting disorder of adipose tissues that leads to profound weight loss and frailty. One key characteristic of cachexia is elevated resting energy expenditure, which has been linked to increased fat lipolysis and thermogenesis.
2024-07-23 | GSE239524 | GEO
Project description:Cachexia is a wasting disorder of adipose tissues that leads to profound weight loss and frailty. One key characteristic of cachexia is elevated resting energy expenditure, which has been linked to increased fat lipolysis and thermogenesis. Extracellular vesicles (EVs) are serving as new messengers to mediate cell-cell communication in vivo. How tumors induce brown fat activity is unknown. Here, we found that breast cancer increased hypoxia inducible factor 1 subunit alpha (HIF1A) protein modification through extracellular-vesicle-encapsulated miR-204 targeting von Hippel-Lindau tumor suppressor (VHL), plays an important role in wasting by driving lipolysis and thermogenic gene expression in adipose tissues.
2023-07-13 | GSE222380 | GEO
Project description:White fat browning is a highly variable genetic trait in mice (Guerra et al., 1998). To gain an overview of strain variations in browning capacities, we performed transcriptome analysis of white fat browning in (1) 5 inbred mouse strains (C57BL/6J, 129S6sv/ev, A/J, AKR/J, and SWR/J) with distinct browning propensities in WAT, and (2) F1 hybrids derived from a high (129S6sv/ev) and low browning strain (C57BL/6J) cross. White fat browning is a highly variable genetic trait in mice (Guerra et al., 1998). To gain an overview of strain variations in browning capacities, we performed transcriptome analysis of white fat browning in three genetic models (Figure 1A), including (1) 5 inbred mouse strains (C57BL/6J, 129S6sv/ev, A/J, AKR/J, and SWR/J) with distinct browning propensities in WAT, (2) F1 hybrids derived from a high (129S6sv/ev) and low browning strain (C57BL/6J) cross.
2019-11-01 | E-MTAB-8344 | biostudies-arrayexpress
Project description:Cancer cachexia (CC) is a poorly understood cause of morbidity and mortality, which has no efficacious treatment or generally-accepted management strategy. The consensus definition for CC identified skeletal muscle loss as a key marker in the diagnosis and classification of cachexia. The importance of fat wasting however, is less understood. During cachexia, different adipose depots demonstrate differential wasting rates. Studies from animal models have suggested adipose tissue may be a key driver of muscle wasting through fat-muscle crosstalk but human studies in this area are lacking. We performed global gene expression profiling of intra-abdominal (IAAT) and subcutaneous (SAT) adipose from weight stable and cachectic cancer patients and healthy controls. Cachexia was defined as >2% weight loss plus low CT-muscularity. Biopsies of SAT and IAAT were taken from patients undergoing resection for oesophago-gastric cancer, and healthy controls (donor nephrectomy) (n=16 and 8 respectively). RNA was isolated and reverse transcribed. cDNA was hybridised to the Affymetrix Clariom S Microarray and data was analysed using R/Bioconductor. Differential expression of genes was assessed using empirical Bayes and moderated-t-statistic approaches. Category enrichment analysis was used with a tissue-specific background to examine the biological context of differentially expressed genes. Selected differentially regulated genes were validated by qPCR. ELISA for Intelectin-1 was performed on IAAT samples for the corresponding patients. The current cohort plus 12 additional patients from each group also had plasma Intelectin-1 ELISA carried out. In IAAT versus SAT comparisons there were 2101, 1722 and 1659 significantly regulated genes in the cachectic, weight stable and control groups respectively. There were 2200 significantly regulated genes from IAAT in cachectic patients compared to controls and 1253 significantly regulated genes from IAAT in weight stable cancer patients compared to controls. The gene showing the largest difference in expression was Intelectin-1 (Omentin-1) (FDR corrected p=0.0001); a novel adipocytokine associated with weight loss in other groups. Genes involving inflammation were enriched in cancer and control IAAT versus SAT though different groups of genes contributed. Energy metabolism and fat browning genesets were downregulated in cancer IAAT as were key fat browning genes (e.g. UCP1). SAT and IAAT have unique gene expression signatures. IAAT is metabolically active in cancer, and maybe a target for therapeutic manipulation. IAAT may play a fundamental role in cachexia, but the downregulation of energy metabolism genes implies a limited role for fat browning in human cachectic patients, in contrast to pre-clinical models.
2020-05-29 | GSE131835 | GEO
Project description:White fat browning is a highly variable genetic trait in mice (Guerra et al., 1998). To gain an overview of strain variations in browning capacities, we performed transcriptome analysis of white fat browning in (1) 5 inbred mouse strains (C57BL/6J, 129S6sv/ev, A/J, AKR/J, and SWR/J) with distinct browning propensities in WAT, and (2) F1 hybrids derived from a high (129S6sv/ev) and low browning strain (C57BL/6J) cross. From our analyses, several transcription factors emerged as novel regulators of white fat browning, including the TFs Zfp521, Fhl1, and Mxd1. We further validated the role of these TFs and performed 3' RNA-seq experiments upon their knockdown, in order to characterize their mechanism of action.
2019-11-01 | E-MTAB-8343 | biostudies-arrayexpress
Project description:Background: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of amiloride for ameliorating muscle wasting in murine models of cancer cachexia. Methods: CT26 and LLC tumor cells were subcutaneously injected into mice to induce cancer cachexia. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 and LLC models, respectively, were characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius. Results: The CT26 and LLC models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. The CT26 and LLC cachexia mice showed increased particle density of plasma exosomes which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius. Conclusions: Our results demonstrated the efficacy of amiloride in ameliorating cachectic muscle wasting and elucidated the underlying mechanistic rationale for its use as an alternative strategy to improve CAC treatments.
2021-07-14 | GSE173250 | GEO
Project description:Here, we investigate the systematic impact of tumor cachexia on muscle function. From a nutritional supplementation perspective, we examine the influence of fatty acid metabolism on the cachectic state, revealing that dietary supplementation with high-fat diet does not alleviate the muscle and fat dysfunction induced by tumors but instead accelerates muscle degradation. Utilizing RNA-seq transcriptome data from muscle tissue, we identify metabolic abnormalities in muscle during cachexia, with the PDK4 gene being activated initially and showing significant enrichment of PPARδ targets. We find that inhibiting PDK4 can mitigate the cachectic state and observe a relationship between the activation of muscle PDK4 and PPARδ during cachexia. This is supported by epigenomic data revealing that PDK4 is a transcriptional target gene of PPARδ in muscle. Activation and mechanical modulation of PPARδ in vivo significantly impact muscle atrophy caused by cachexia. Our research suggests that targeting PPARδ could serve as a therapeutic drug target for tumor cachexia.
2024-12-18 | GSE246122 | GEO
Project description:Cancer cachexia is a multifactorial metabolic syndrome defined by the rapid loss of skeletal muscle mass and the loss of fat mass. Up 80% of cancer patients at the late stage with cachexia suffer from progressive atrophy of adipose tissue. Unlike studies on skeletal muscle wasting, there is limited research on fat loss in cachexia. It was noted that most patients suffer from fat loss as cancer progress. Fat loss precedes muscle loss, is associated with shorter survival, and is variable to timing and intensity in various cancer populations. Increased lipolysis may be the leading cause of fat loss in cancer cachexia. miRNAs are a class of non-coding RNAs of 19~25 nucleotides that regulate gene silencing by interacting with the 3’ untranslated region (UTR) of target mRNA to cause mRNA degradation and translational repression. miRNAs play multifaceted roles in pancreatic cancer proliferation, survival, metastasis, and chemoresistance. Aberrant expression of miRNA in circulating exosomes may play potential roles in modulating fat loss in cancer cachexia. We identified 2 miRNAs, miR-16 and miR-29, which have 2-fold higher expression existed in at PDAC cells. To explore which genes in adipogenesis and lipolysis were directly affected by miR-16-5p or/and miR-29a-3p, we analyzed the targets which were down-regulated in both miR-16-5p and miR-29a-3p-transfected 3T3-L1 cells by mass analysis.
2024-06-13 | PXD037998 | Pride