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Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network in exosomes from lipoma tissue reveals differential impacts on biological functions

ABSTRACT: We previously showed that both exosomes from lipoma tissue (Exo-LT) and exosomes from adipose tissue (Exo-AT) promoted the proliferation, migration, and adipogenesis of ADSCs. There was no significant difference between Exo-LT and Exo-AT in promoting adipogenesis in ADSCs, but Exo-LT had a stronger ability to promote the proliferation and migration of ADSCs than Exo-AT. To understand the mechanism behind the stronger proliferative effects of Exo-LT than Exo-AT, we explored the differential gene expression pattern between Exo-LT and Exo-AT. Using high-throughput sequencing technology, we analyzed the expression of lncRNA, miRNA, and mRNA in Exo-LT and Exo-AT and identified the significantly differentially expressed genes, and then searched for mRNAs related to cell proliferation and adipogenesis in GO enrichment and KEGG pathway analysis results for subsequent targeted analysis and construction of ceRNA networks. A total of 10 mRNAs were identified, which met both significant differential expression conditions (|logFC|>2, p<0.05) and abundance quality control (CPM＞100). Of these, 6 were found to be up-regulated in Exo-LT and 4 were down-regulated in Exo-LT. Afterwards in the ceRNA regulatory network, we noticed 5 meaningful lncRNAs that were highly correlated with cell proliferation and adipogenesis, including HOXA11-AS, GAS5, HOTAIR, MALAT1, and PVT1. HOXA11-AS was significantly up-regulated in Exo-LT, while GAS5, HOTAIR, MALAT1, and PVT1 were expressed at high levels in both the Exo-LT and Exo-AT group. Interestingly, our follow-up analysis showed that many of the lncRNA-miRNA targeting relationships predicted by these 5 lncRNAs in the ceRNA network were already validated in a large number of previous studies. Our analysis of lncRNA, miRNA, and mRNA expression profiles and ceRNA networks in Exo-LT provides a preliminary explanation for the differences between Exo-LT and Exo-AT in promoting ADSCs proliferation and adipogenesis, as well as a new theoretical basis explaining the mechanism of lipoma tissue formation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229286 | GEO | 2026/04/30

REPOSITORIES: GEO

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Project description:Adipogenesis occurs through a specific gene program in undifferentiated fat progenitors. We hypothesized that the properties of the fat progenitors are regulated by hox genes, the developmental genes essential in different tissue stem cells. Their biased expression in white and brown fat implies roles in distinguishing the two fat types. Among 39 Hox genes, Hoxc8 is highly enriched in undifferentiated adipose tissue stem cells (ADSCs) and down-regulated in differentiated adipocytes. Forced expression of Hoxc8 suppressed adipocyte differentiation of ADSCs. Using microarrays, we investigated the effect of Hoxc8 overexpression on global transcripts in ADSCs. We compared among four groups: untreated ADSCs, adipogenic induction media (MDI)-treated ADSCs, MDI-treated ADSC-vector and MDI-treated ADSC-Hoxc8. A number of, but not all, adipogenesis-related genes are suppressed by Hoxc8. This dataset illustrates the global effect of Hoxc8, a developmental transcription factor, on the expression of adipogenesis-related genes. Gene expression was compared among untreated ADSCs (control), adipogenic induction media-treated ADSCs, adipogenic induction media-treated ADSC-vector (ADSCs transduced with control vector), and adipogenic induction media-treated ADSC-Hoxc8 (ADSCs transduced with human Hoxc8). Total RNA was isolated from ADSCs using the Qiagen RNeasy kit (Qiagen). At NimbleGen, quality and yield were verified before cDNA synthesis and Cy3-end labeling. The labeled cDNA samples were hybridized to Homo sapiens 4-Plex arrays (Roche NimbleGen, A4487001-00-01) that represent 24,000 human genes. Raw data files for each sample were normalized and background-corrected using a Robust Multi-Array Analysis as implemented by NimbleScan software. Students’ two-tail t-tests were conducted among the samples for each transcript and fold-change was determined. Transcripts whose abundance was significantly altered (P < 0.05) and an absolute fold change greater than 2 were defined as differentially regulated.

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Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network in exosomes from lipoma tissue reveals differential impacts on biological functions

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