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Lin28 enhances de novo fatty acid synthesis to promote cancer progression via SREBP ‐1
Author(s) -
Zhang Yang,
Li Chenchen,
Hu Chuanzhen,
Wu Qian,
Cai Yongping,
Xing Songge,
Lu Hui,
Wang Lin,
Huang De,
Sun Linchong,
Li Tingting,
He Xiaoping,
Zhong Xiuying,
Wang Junfeng,
Gao Ping,
Smith Zachary J,
Jia Weidong,
Zhang Huafeng
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948115
Subject(s) - sterol regulatory element binding protein , fatty acid , fatty acid synthesis , lin28 , biology , chemistry , biochemistry , microbiology and biotechnology , cancer research , cholesterol , gene , sterol , transcription factor , sox2
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 mRNA s 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.