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MiR-422a regulates cellular metabolism and malignancy by targeting pyruvate dehydrogenase kinase 2 in gastric cancer.

Abstract：

:Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays a crucial role in human malignancies. Here, we showed that microRNA-422a (miR-422a) expression was dramatically downregulated in gastric cancer (GC) samples and cell lines compared with normal controls, and that its expression level was inversely related to tumor size and depth of infiltration. Functional studies revealed that the overexpression of miR-422a in GC tumor cells suppressed cell proliferation and migration, and drove a metabolic shift from aerobic glycolysis to oxidative phosphorylation. Mechanistic analysis suggested that miR-422a repressed pyruvate dehydrogenase kinase 2 (PDK2) to restore activity of the pyruvate dehydrogenase (PDH), the gatekeeping enzyme that catalyzes the decarboxylation of pyruvate to produce acetyl-CoA. Importantly, we further demonstrated that the mir-422a-PDK2 axis also influenced another metabolic pathway, de novo lipogenesis in cancer cells, and that it subsequently affected reactive oxygen species (ROS) and RB phosphorylation levels, ultimately resulting in cell cycle arrest in G1 phase. Our findings show that the miR-422a-PDK2 axis is an important mediator in metabolic reprogramming and a promising therapeutic target for antitumor treatment.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

He Z,Li Z,Zhang X,Yin K,Wang W,Xu Z,Li B,Zhang L,Xu J,Sun G,Wang L,Li Q,Huang X,Zhang L,Zhang D,Xu H,Xu Z

doi

10.1038/s41419-018-0564-3

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

505

issue

5

issn

2041-4889

pii

10.1038/s41419-018-0564-3

journal_volume

9

pub_type

杂志文章

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