MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes

• Published in: Journal of animal science and biotechnology 2021-02, Vol.12 (1), p.12-12, Article 12
• Main Authors: Zhang, Que, Cai, Rui, Tang, Guorong, Zhang, Wanrong, Pang, Weijun
• Format: Article
• Language: English
• Subjects: Adapter proteins; Adipogenesis; Adipose tissue; AKT protein; AKT/mTORC1 signal pathway; Antibodies; Biomarkers; Biotechnology; Body fat; Cell cycle; Cell differentiation; Cell growth; Cell proliferation; Cyclin-dependent kinases; Differentiation; Gene expression; Hogs; Kinases; MiR-146a-5p; miRNA; Porcine intramuscular fat; Pork; Preadipocytes; Quality assessment; Regulatory mechanisms (biology); Sequence analysis; Signal transduction; Signaling; Smad protein; SMAD4; Smad4 protein; TGF-β signal pathway; Tissue analysis; TRAF6 protein; Transforming growth factor-b; Tumor necrosis factor receptors
• ISSN: 1674-9782; 2049-1891; 2049-1891
• DOI: 10.1186/s40104-020-00525-3

Intramuscular fat (IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation. By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6 (TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway. MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.