miR-424 Promotes Bovine Adipogenesis Through an Unconventional Post-Transcriptional Regulation of STK11

Abstract

Adipose tissue is the largest energy reservoir and secretory organ in the animal body, and is essential for maintaining normal physiological functions and metabolic balance. MicroRNAs regulate the process of adipogenic differentiation through posttranscriptional regulatory mechanisms. In the present study, miR-424 was upregulated during bovine adipocyte differentiation both in vivo and in vitro. The overexpression and interference of miR-424 exhibited the positive regulatory role in the differentiation of bovine adipocytes. Furthermore, miR-424 directly binds to the three prime untranslated region (3' UTR) of serine/threonine kinase 11 (STK11, also called LKB1), a master upstream gene in the AMP-activated protein kinase (AMPK) cascade, and up-regulates its expression. Functional studies showed that the knockdown of STK11 attenuated the pro-adipogenic effect of miR-424. Post-transcriptional regulation of STK11 by miR-424 was mediated potentially in an RNA binding protein (RBP) binding site-dependent manner. In conclusion, our study shows that miR-424 promotes bovine adipogenesis through an unconventional post-transcriptional regulation of STK11, which may serve as a potential target for the regulation of bovine adipogenesis and the improvement of livestock breeding efficiency.

RNA-Seq Reveals Function of Bta-miR-149-5p in the Regulation of Bovine Adipocyte Differentiation

“…High-throughput sequencing and microarray analysis revealed the roles of novel miRNAs in animals [ 53 ]. Previously, the roles of let-7 [ 54 ], miR-21a [ 55 ], miR-23a [ 56 , 57 ], miR-27a/b [ 58 , 59 ], miR-130 [ 60 ], miR-185 [ 61 ], miR-448 [ 62 ], and miR-709 [ 63 ] in lipogenesis negatively regulated adipocyte differentiation, whereas miR-21 [ 64 , 65 ], miR-26b [ 66 ], miR-143 [ 67 ], miR-148 [ 68 ], miR-183 [ 69 ], miR-424 [ 14 ], and miR-425 [ 70 ] positively regulated adipocyte differentiation. Previously, we confirmed the role of bta-miR-149-5p bovine adipocyte proliferation and differentiation [ 32 ].…”

“…Moreover, miR-144-3p suppresses preadipocyte proliferation [ 13 ]. The role of miR-424 in bovine adipogenesis through direct regulation of serine/threonine kinase 11 (STK11 also known as LKB1) was also identified through regulation of AMP-activated protein kinase (AMPK) [ 14 ]. Similarly, miR-17-92, miR-27, miR-93, miR-130, and miR-378 are key regulators of adipogenesis through adipocyte proliferation or differentiation [ 15 , 16 , 17 , 18 ].…”

Integrated microRNA–mRNA analysis reveals the roles of microRNAs in the muscle fat metabolism of Yanbian cattle

“…Wang et al. also showed that miR‐424 was upregulated during and promoted bovine adipogenesis via unconventional posttranscriptional regulation of STK11 in 2020 (Wang et al ., 2020a,b). Additionally, Oliveira et al .…”

Bta-miR-376a Targeting KLF15 Interferes with Adipogenesis Signaling Pathway to Promote Differentiation of Qinchuan Beef Cattle Preadipocytes

“…Many regulatory factors associated with adipogenesis, as well as regulatory methods of epigenetics and miRNA, have been identified [ 28 , 29 , 30 , 31 ]. Several novel miRNA have been identified using microarray analysis and high-throughput sequencing [ 32 ]: miR-424 [ 33 ], miR-210 [ 34 ], miR-26a [ 35 ], miR-17-5p [ 36 ], miR-152 [ 37 ], miR-143 [ 38 ], and miR-519d [ 39 ] reduce adipogenesis by positively facilitating adipocyte differentiation, whereas miR-20a-5p [ 40 ], miR-130a/b [ 23 ], miR-27a/b [ 41 , 42 ], and miR-155 [ 43 ] negatively regulate adipocyte differentiation. The expression of bta-miR-376a differs among bovine tissues and is tissue-specific.…”