Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking

Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

PLoS biology - 16(2018), 10 vom: 19. Okt., Seite e2006483

Sprache:

Englisch

Beteiligte Personen:

Jin, Guang-Zhi [VerfasserIn]
Zhang, Yajuan [VerfasserIn]
Cong, Wen-Ming [VerfasserIn]
Wu, Xueyuan [VerfasserIn]
Wang, Xiongjun [VerfasserIn]
Wu, Siyang [VerfasserIn]
Wang, Siyao [VerfasserIn]
Zhou, Weiping [VerfasserIn]
Yuan, Shengxian [VerfasserIn]
Gao, Hong [VerfasserIn]
Yu, Guanzhen [VerfasserIn]
Yang, Weiwei [VerfasserIn]

Links:

Volltext

Themen:

CNBP protein, human
EC 5.4.2.2
FOXJ2 protein, human
Forkhead Transcription Factors
Glucose
IY9XDZ35W2
Journal Article
PGM1 protein, human
Phosphoglucomutase
RNA-Binding Proteins
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 06.05.2019

Date Revised 06.05.2019

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pbio.2006483

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM289702909