miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling

Abstract

MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as post-transcriptional regulators of fat development and adipogenesis. Adipogenic marker genes, such as CCAAT/enhancer binding protein a (Cebpa), peroxisome proliferatoractivated receptor g (Pparg), adipocyte fatty acid binding protein (Ap2), and fatty acid synthase (Fas), are regarded as the essential transcriptional regulators of preadipocyte differentiation and lipid storage in mature adipocytes. Canonical Wnt/b-catenin signaling is recognized as a negative molecular switch during adipogenesis. In the present work we found that miR-135a-5p is markedly downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-135a-5p impairs the expressions of adipogenic marker genes as well as lipid droplet accumulation and triglyceride content, indicating the importance of miR-135a-5p for adipogenic differentiation and adipogenesis. Further studies show that miR-135a-5p directly targets adenomatous polyposis coli (Apc), contributes to the translocation of b-catenin from cytoplasm to nucleus, and then activates the expressions of cyclin D1 (Ccnd1) and Cmyc, indicating the induction of canonical Wnt/b-catenin signaling. In addition, inhibition of APC with siRNA exhibits the same effects as overexpression of miR-135a-5p. Our findings demonstrate that miR-135a-5p suppresses 3T3-L1 preadipocyte differentiation and adipogenesis through the activation of canonical Wnt/b-catenin signaling by directly targeting Apc. Taken together, these results offer profound insights into the adipogenesis mechanism and the development of adipose tissue.

Syngeneic Cardiac and Bone Marrow Stromal Cells Display Tissue-Specific microRNA Signatures and microRNA Subsets Restricted to Diverse Differentiation Processes

“…Consistently, miR-27b, which was also up-regulated by AM in CStC, has been shown to have an enhanced myocardial expression during heart development [51], and to impair human adipocyte differentiation by targeting PPARγ [52]. On the other hand, miR-135a-5p suppressed 3T3-L1 preadipocyte differentiation and adipogenesis through the activation of canonical Wnt/β-catenin signaling [53]. Overexpression of miR-142, another miR that we found upregulated by AM in CStC, has been shown to be inversely related to MAPK activity in cultured cardiac myocytes, inhibiting both survival and growth pathways and repressing multiple components of the NF-κB pathway, and to induce extensive apoptosis and cardiac dysfunction in a model of cardiac hypertrophy [54].…”

microRNA regulation of Wnt signaling pathways in development and disease

“…Several miRNAs have been identified to activate the Wnt signaling pathway which promotes osteoblast differentiation. miR-27, miR-142-3p, and miR-135a-5p target APC which leads to accumulation of β-catenin and activation of Wnt signaling to promote osteoblast differentiation in human fetal osteoblastic 1.19 (hFOB1.19) and 3T3-L1 cells [231–233]. miR-29 participates in the fine-tuning of Wnt signaling such that the canonical Wnt signaling induces miR-29a transcription which down regulates inhibitors of canonical Wnt signaling such as DKK1 , Kremen2 , and SFRP2 to promote osteoblast differentiation in hFOB1.19 cells [234].…”

MicroRNA-125b-5p inhibits proliferation and promotes adipogenic differentiation in 3T3-L1 preadipocytes

“…For example, miR-21, miR-143, miR-26b, and miR-210 accelerate 3T3-L1 adipogenic differentiation [13][14][15][16][17], while miR-130, miR-135a-5p, and the miR-27 family impair preadipocyte differentiation [18][19][20][21]. In addition, many miRNAs, such as miR-21, miR-143, and miR-let-7, have been reported to be involved in adipocyte proliferation [22][23][24].…”