The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • G. Li
  • M. Li
  • J. Hu
  • R. Lei
  • H. Xiong
  • H. Ji
  • Q. Wei
  • G. Hu

Detail(s)

Original languageEnglish
Pages (from-to)989-998
Journal / PublicationOncogene
Volume36
Issue number7
Publication statusPublished - 16 Feb 2017
Externally publishedYes

Abstract

Reprogrammed metabolism is one of the hallmarks of cancer. The dysregulation of glycolysis in cancer has been heavily studied. However, it remains largely unclear how other metabolic processes are regulated in cancer cells. Here we show that microRNA-182 (miR-182) suppresses pyruvate dehydrogenase (PDH) kinase 4 (PDK4) and promotes lung tumorigenesis. miR-182 is dysregulated and inversely correlated with PDK4 in human lung adenocarcinomas. The miR-182-PDK4 axis regulates lung cancer cell growth by modulating the activity of PDH, the gatekeeping enzyme of pyruvate flux into acetyl-CoA, and subsequently de novo lipogenesis of cancer cells. Suppression of lipogenesis by silencing ATP citrate lyase (ACLY) and fatty acid synthase (FASN) or by chemical inhibitors diminishes the effects of miR-182-PDK4 in tumor growth. Alteration of de novo lipogenesis also affects reactive oxygen species (ROS) production and the downstream JNK signaling pathway. Hence, our work suggests that the miR-182-PDK4 axis is a crucial regulator of cancer cell metabolism and a potential target for antitumor therapy. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Bibliographic Note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to lbscholars@cityu.edu.hk.

Citation Format(s)

The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis. / Li, G.; Li, M.; Hu, J. et al.
In: Oncogene, Vol. 36, No. 7, 16.02.2017, p. 989-998.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review