Lin28 通过 SREBP-1 增强从头合成脂肪酸以促进癌症进展。
Lin28 enhances de novo fatty acid synthesis to promote cancer progression via SREBP-1.
机构信息
Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Department of General Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Molecular Medicine, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
出版信息
EMBO Rep. 2019 Oct 4;20(10):e48115. doi: 10.15252/embr.201948115. Epub 2019 Aug 5.
Lin28 plays an important role in promoting tumor development, whereas its exact functions and underlying mechanisms are largely unknown. Here, we show that both human homologs of Lin28 accelerate de novo fatty acid synthesis and promote the conversion from saturated to unsaturated fatty acids via the regulation of SREBP-1. By directly binding to the mRNAs of both SREBP-1 and SCAP, Lin28A/B enhance the translation and maturation of SREBP-1, and protect cancer cells from lipotoxicity. Lin28A/B-stimulated tumor growth is abrogated by SREBP-1 inhibition and by the impairment of the RNA binding properties of Lin28A/B, respectively. Collectively, our findings uncover that post-transcriptional regulation by Lin28A/B enhances de novo fatty acid synthesis and metabolic conversion of saturated and unsaturated fatty acids via SREBP-1, which is critical for cancer progression.
Lin28 在促进肿瘤发展中发挥重要作用，但其确切功能和潜在机制在很大程度上尚不清楚。在这里，我们发现人类 Lin28 同源物均能通过 SREBP-1 的调控促进从头脂肪酸合成，并促进饱和脂肪酸向不饱和脂肪酸的转化。Lin28A/B 通过直接结合 SREBP-1 和 SCAP 的 mRNA，增强 SREBP-1 的翻译和成熟，并保护癌细胞免受脂毒性。SREBP-1 抑制和 Lin28A/B 的 RNA 结合特性受损分别削弱了 Lin28A/B 刺激的肿瘤生长。总之，我们的研究结果揭示了 Lin28A/B 通过 SREBP-1 进行的转录后调节增强了从头脂肪酸合成和饱和及不饱和脂肪酸的代谢转化，这对癌症进展至关重要。
Zotero 插件