Department of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan, Guangdong, 523808, China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
Department of Pharmacology, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
Biochem Biophys Res Commun. 2019 Apr 16;511(4):753-758. doi: 10.1016/j.bbrc.2019.02.133. Epub 2019 Mar 1.
Long non-coding RNAs (lncRNAs) have gained extensive attentions due to their significant roles in diverse biological process. However, the potential functions of lncRNAs participation in adipocyte differentiation have not been fully explored. Here we identified a long non-coding RNA called lnc-OAD (lncRNA associated with osteoblast and adipocyte differentiation, transcribed from 1700018A04Rik gene), which modulated 3T3-L1 adipocyte differentiation. Lnc-OAD was up-regulated expression during 3T3-L1 differentiation and stable knockdown of lnc-OAD inhibited adipocyte differentiation in 3T3-L1 cells. Further mechanisms study revealed that silencing of lnc-OAD strongly elevated the protein expression of β-catenin, and then decreased expression of adipocyte master transcription factors PPAR-γ and C/EBPα. The addition of IWR-1 up-regulated the expression of PPAR-γ and C/EBPα and rescued the impairment of adipocyte differentiation caused by lnc-OAD knockdown. Meanwhile, we also found mitotic clonal expansion (MCE) during the early stage of adipocyte differentiation was inhibited in lnc-OAD-knockdown cells. Taken together, our study reveals a novel function of lnc-OAD in modulating adipogenesis via influencing mitotic clonal expansion and regulating WNT/β-catenin signaling pathway.
长链非编码 RNA（lncRNA）因其在多种生物过程中发挥的重要作用而受到广泛关注。然而，lncRNA 参与脂肪细胞分化的潜在功能尚未得到充分探索。在这里，我们鉴定了一种长链非编码 RNA，称为 lnc-OAD（与成骨细胞和脂肪细胞分化相关的长链非编码 RNA，由 1700018A04Rik 基因转录），它调节 3T3-L1 脂肪细胞分化。lnc-OAD 在 3T3-L1 分化过程中表达上调，稳定敲低 lnc-OAD 可抑制 3T3-L1 细胞中的脂肪细胞分化。进一步的机制研究表明，沉默 lnc-OAD 可强烈上调β-catenin 的蛋白表达，进而降低脂肪细胞主转录因子 PPAR-γ 和 C/EBPα 的表达。添加 IWR-1 可上调 PPAR-γ 和 C/EBPα 的表达，并挽救由 lnc-OAD 敲低引起的脂肪细胞分化受损。同时，我们还发现 lnc-OAD 敲低细胞中的有丝分裂克隆扩张（MCE）在脂肪细胞分化的早期阶段受到抑制。总之，我们的研究揭示了 lnc-OAD 通过影响有丝分裂克隆扩张和调节 WNT/β-catenin 信号通路来调节脂肪生成的新功能。
