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Lnc RNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism
Author(s) -
Zheng Xin,
Han Han,
Liu GuangPing,
Ma YanXiu,
Pan RuoLang,
Sang LingJie,
Li RuiHua,
Yang LuoJia,
Marks Jeffrey R,
Wang Wenqi,
Lin Aifu
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797609
Subject(s) - biology , hippo signaling pathway , microrna , effector , hedgehog , glycolysis , microbiology and biotechnology , hedgehog signaling pathway , signal transduction , cancer research , transcription factor , carcinogenesis , rna , long non coding rna , cancer , metabolism , biochemistry , genetics , gene
The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes‐associated protein ( YAP ). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNA s (lnc RNA s) as attractive therapeutic targets, given their roles in modulating various cancer‐related signaling pathways. In this study, we report that lnc RNA breast cancer anti‐estrogen resistance 4 ( BCAR 4) is required for YAP ‐dependent glycolysis. Mechanistically, YAP promotes the expression of BCAR 4, which subsequently coordinates the Hedgehog signaling to enhance the transcription of glycolysis activators HK 2 and PFKFB 3. Therapeutic delivery of locked nucleic acids ( LNA s) targeting BCAR 4 attenuated YAP ‐dependent glycolysis and tumor growth. The expression levels of BCAR 4 and YAP are positively correlated in tissue samples from breast cancer patients, where high expression of both BCAR 4 and YAP is associated with poor patient survival outcome. Taken together, our study not only reveals the mechanism by which YAP reprograms glucose metabolism, but also highlights the therapeutic potential of targeting YAP ‐ BCAR 4‐glycolysis axis for breast cancer treatment.