A Novel lnc-RNA, Named lnc-ORA, Is Identified by RNA-Seq Analysis, and Its Knockdown Inhibits Adipogenesis by Regulating the PI3K/AKT/mTOR Signaling Pathway

Abstract

Obesity is closely associated with numerous adipogenic regulatory factors, including coding and non-coding genes. Long noncoding RNAs (lncRNAs) play a major role in adipogenesis. However, differential expression profiles of lncRNAs in inguinal white adipose tissue (iWAT) between wild-type (WT) and ob/ob mice, as well as their roles in adipogenesis, are not well understood. Here, a total of 2809 lncRNAs were detected in the iWAT of WT and ob/ob mice by RNA-Sequencing (RNA-Seq), including 248 novel lncRNAs. Of them, 46 lncRNAs were expressed differentially in WT and ob/ob mice and were enriched in adipogenesis signaling pathways as determined by KEGG enrichment analysis, including the PI3K/AKT/mTOR and cytokine–cytokine receptor interaction signaling pathways. Furthermore, we focused on one novel lncRNA, which we named lnc-ORA (obesity-related lncRNA), which had a seven-fold higher expression in ob/ob mice than in WT mice. Knockdown of lnc-ORA inhibited preadipocyte proliferation by decreasing the mRNA and protein expression levels of cell cycle markers. Interestingly, lnc-ORA knockdown inhibited adipocyte differentiation by regulating the PI3K/AKT/mTOR signaling pathway. In summary, these findings contribute to a better understanding of adipogenesis in relation to lncRNAs and provide novel potential therapeutic targets for obesity-related metabolic diseases.

miR‑139‑5p affects cell proliferation, migration and adipogenesis by targeting insulin‑like growth factor 1 receptor in hemangioma stem cells

“…Numerous studies have revealed the crucial function of the PI3K/AKT signaling cascade during adipogenesis (35)(36)(37)(38)(39). For example, the PI3K/AKT signaling pathway mediated by insulin may result in excessive lipids in adipose tissue, so it serves a crucial function in the adipose cells of patients with obesity (40). A previous study revealed that IGF-1 upregulated the phosphorylation of AKT through the IGF-1R-PI3K signaling pathway, which ultimately induced the differentiation of HemScs into adipocytes (6).…”

Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

“…The KEGG pathway enrichment analysis of target genes revealed a total of 47 annotated pathways (Additional le 7: Table S7B), of these pathways, three were signi cantly enriched (P<0.05), namely Tight junction(ko04530), Glycosaminoglycan biosynthesisheparan sulfate/heparin(ko00534) and Lysosome(ko04142). Although some pathways were not signi cantly enriched, such as Wnt signaling pathway(ko04310), AMPK signaling pathway(ko04152), mTOR signaling pathway(ko04150), Cell adhesion molecules (CAMs)(ko04514) and MAPK signaling pathway(ko04010) and Jak-STAT signaling pathway , these pathways have been reported in the literature to play an important role in lipid deposition [36][37][38][39][40][41]. Overall, the signi cantly enriched pathways and GO terms involve 49 target genes.…”

Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

“…Among them, eight pathways were related to lipid deposition and metabolism, including alpha-Linolenic acid metabolism (ko00592), FoxO signaling pathway (ko04068), Biosynthesis of unsaturated fatty acids (ko01040), Cell adhesion molecules (ko04514), Phosphonate and phosphinate metabolism (ko00440), Ether lipid metabolism (ko00565), Tight junction (ko04530) and Arachidonic acid metabolism (ko00590). Although some pathways were not signi cantly enriched, such as PPAR, Wnt, AMPK and mTOR signaling pathways, these pathways still played an important role in lipid deposition [31,[34][35][36]. Overall, the KEGG enrichment analysis of target genes revealed 16 critical pathways with 17 target genes (Table 3).…”