Genome-Wide Expression Profiling and Networking Reveals an Imperative Role of IMF-Associated Novel CircRNAs as ceRNA in Pigs

Abstract

Intramuscular fat (IMF) deposition is a biological process that has a strong impact on the nutritional and sensorial properties of meat, with relevant consequences on human health. Pork loins determine the effects of marbling on the sensory attributes and meat quality properties, which differ among various pig breeds. This study explores the crosstalk of non-coding RNAs with mRNAs and analyzes the potential pathogenic role of IMF-associated competing endogenous RNA (ceRNA) in IMF tissues, which offer a framework for the functional validation of key/potential genes. A high-throughput whole-genome transcriptome analysis of IMF tissues from longissimus dorsi muscles of Large White (D_JN) and Laiwu (L_JN) pigs resulted in the identification of 283 differentially expressed circRNAs (DECs), including two key circRNAs (circRNA-23437, circRNA-08840) with potential binding sites for multiple miRNAs regulating the whole network. The potential ceRNA mechanism identified the DEC target miRNAs-mRNAs involved in lipid metabolism, fat deposition, meat quality, and metabolic syndrome via the circRNA-miRNA-mRNA network, concluding that ssc-mir-370 is the most important target miRNA shared by both key circRNAs. TGM2, SLC5A6, ECI1, FASN, PER1, SLC25A34, SOD1, and COL5A3 were identified as hub genes through an intensive protein-protein interaction (PPI) network analysis of target genes acquired from the ceRNA regulatory network. Functional enrichments, pathway examinations, and qRT-PCR analyses infer their implications in fat/cholesterol metabolism, insulin secretion, and fatty acid biosynthesis. Here, circRNAs and miRNA sequencing accompanied by computational techniques were performed to analyze their expressions in IMF tissues from the longissimus dorsi muscles of two pig breeds. Their target gene evolutionary trajectories, expression profiling, functional enrichments, subcellular localizations, and structural advances with high-throughput protein modeling, following genomic organizations, will provide new insights into the underlying molecular mechanisms of adipocyte differentiation and IMF deposition and a much-needed qualitative framework for future research to improve meat quality and its role as a biomarker to treat lipid metabolic syndromes.