10.1371/journal.pone.0086872PLoS ONE91-POLN

A Jemal

AM Liu

Angela M. Liu

B Chaneton

C Coulouarn

CJ David

CJ Jung

D Anastasiou

DR Boutz

Felix H. Shek

HR Christofk

J Burchard

Jin Q. Cheng

Jinfei Chen

John M. Luk

K Kitamura

Kwong-Fai Wong

L Lv

LX Liu

MG Vander Heiden

MJ Walsh

MZ Xu

Nikki P. Lee

O Warburg

Q Sun

Ronnie T. Poon

S Bai

T Hitosugi

W Yang

WC Tsai

Zhi Xu

PLoS ONE

PubMed

Liu Angela M.

Xu Zhi

Shek Felix H.

Wong Kwong-Fai

Lee Nikki P.

Poon Ronnie T.

Chen Jinfei

Luk John M.

Public Library of Science (PLOS)

miR-122 Targets Pyruvate Kinase M2 and Affects Metabolism of Hepatocellular Carcinoma

In contrast to normal differentiated cells that depend on mitochondrial oxidative phosphorylation for energy production, cancer cells have evolved to utilize aerobic glycolysis (Warburg's effect), with benefit of providing intermediates for biomass production. MicroRNA-122 (miR-122) is highly expressed in normal liver tissue regulating a wide variety of biological processes including cellular metabolism, but is reduced in hepatocellular carcinoma (HCC). Overexpression of miR-122 was shown to inhibit cancer cell proliferation, metastasis, and increase chemosensitivity, but its functions in cancer metabolism remains unknown. The present study aims to identify the miR-122 targeted genes and to investigate the associated regulatory mechanisms in HCC metabolism. We found the ectopic overexpression of miR-122 affected metabolic activities of HCC cells, evidenced by the reduced lactate production and increased oxygen consumption. Integrated gene expression analysis in a cohort of 94 HCC tissues revealed miR-122 level tightly associated with a battery of glycolytic genes, in which pyruvate kinase (PK) gene showed the strongest anti-correlation coefficient (Pearson r = -0.6938, p = <0.0001). In addition, reduced PK level was significantly associated with poor clinical outcomes of HCC patients. We found isoform M2 (PKM2) is the dominant form highly expressed in HCC and is a direct target of miR-122, as overexpression of miR-122 reduced both the mRNA and protein levels of PKM2, whereas PKM2 re-expression abrogated the miR-122-mediated glycolytic activities. The present study demonstrated the regulatory role of miR-122 on PKM2 in HCC, having an implication of therapeutic intervention targeting cancer metabolic pathways

Angela M Liu

Felix H Shek

Nikki P Lee

Ronnie T Poon

John M Luk

Directory of Open Access Journals

miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma.

Crossref

Shek, HP

Liu, ML

Wong, KF

Xu, Z

Luk, JMC

Poon, RTP

Lee, NPY

Chen, J

HKU Scholars Hub

miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma

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http://hub.hku.hk/bitstream/10722/196582/1/Content.pdf

MiR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma

MiR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma

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Public Library of Science (PLOS)

Directory of Open Access Journals

Crossref

Public Library of Science (PLOS)

HKU Scholars Hub