Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1

被引：152

作者：

Ma, Xiaoyu ^{[1
,2
]}

Li, Chenchen ^{[1
,2
]}

Sun, Linchong ^{[1
,2
]}

Huang, De ^{[1
,2
]}

Li, Tingting ^{[1
,2
]}

He, Xiaoping ^{[1
,2
]}

Wu, Gongwei ^{[1
,2
]}

Yang, Zheng ^{[1
,2
]}

Zhong, Xiuying ^{[1
,2
]}

Song, Libing ^{[3
,4
]}

Gao, Ping ^{[1
,2
]}

Zhang, Huafeng ^{[1
,2
]}

机构：

[1] Univ Sci & Technol China, Sch Life Sci, Inst Canc Res, Hefei 230027, Peoples R China

[2] Univ Sci & Technol China, Sch Life Sci, Innovat Ctr Cell Biol, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Peoples R China

[3] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol Southern China, Guangzhou 510060, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510060, Guangdong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

PROMOTES TRANSFORMATION; MYC; LET-7; LIN28; EXPRESSION; HIF-1; IDENTIFICATION; SUPPRESSION; ADAPTATION; METABOLISM;

D O I：

10.1038/ncomms6212

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aberrant expression of Lin28 and let-7 has been observed in many human malignancies. However, its functions and underlying mechanisms remain largely elusive. Here we show that aberrant expression of Lin28 and let-7 facilitates aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we discover that Lin28A and Lin28B enhance, whereas let-7 suppresses, aerobic glycolysis via targeting pyruvate dehydrogenase kinase 1, or PDK1, in a hypoxia-or hypoxia-inducible factor-1 (HIF-1)-independent manner, illustrating a novel pathway to mediate aerobic glycolysis of cancer cells even in ambient oxygen levels. Importantly, we further demonstrate that PDK1 is critical for Lin28A- and Lin28B-mediated cancer proliferation both in vitro and in vivo, establishing a previously unappreciated mechanism by which Lin28/let-7 axis facilitates Warburg effect to promote cancer progression. Our findings suggest a potential rationale to target PDK1 for cancer therapy in malignancies with aberrant expression of Lin28 and let-7.

引用

页数：13

共 38 条

[1] The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans [J].