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Autophagy suppresses proliferation of HepG2 cells via inhibiting glypican-3/wnt/β-catenin signaling

Authors Hu P, Cheng B, He Y, Wei Z, Wu D, Meng Z

Received 31 August 2017

Accepted for publication 2 November 2017

Published 4 January 2018 Volume 2018:11 Pages 193—200

DOI https://doi.org/10.2147/OTT.S150520

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 4

Editor who approved publication: Dr Ingrid Espinoza


Pei Hu,1,2 Bin Cheng,3 Yulin He,3 Zhiqiang Wei,3 Dongfang Wu,1 Zhongji Meng3,4

1Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, 2Department of Clinical Laboratory Medicine, 3Institute of Biomedical Research, 4Department of Infectious Disease, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China

Introduction: Autophagy plays an important role in the growth and survival of hepatocellular carcinoma (HCC) cells through several target proteins or signaling pathways. Glypican-3 (GPC3) is a new reliable HCC marker, which is involved in tumor growth in HCC, primarily mediated by wnt/β-catenin signaling.
Objective: The present study aimed to identify the role of autophagy in the proliferation of HepG2 cells through GPC3/wnt/β-catenin signaling.
Results and discussion: Results demonstrated that induction of autophagy by nutrition starvation and rapamycin treatment led to the downregulation of GPC3 expression in HepG2 cells, accompanied by the decreased expression of wnt downstream target genes (β-catenin, c-myc and cyclin D1). On the other hand, inhibition of autophagy by 3-methyl adenine (3-MA) could rescue rapamycin-directed downregulation of GPC3 and wnt/β-catenin target genes and augment the proliferation of HepG2 cells. Furthermore, interference of GPC3 by siRNA suppressed wnt/β-catenin signaling and attenuated 3-MA stimulation of HepG2 cell proliferation. More interestingly, the mRNA of GPC3 remained unchanged when the protein levels of GPC3 were decreased by autophagy activation, suggesting that induction of autophagy may accelerate the degradation of GPC3.
Conclusion: These results suggest that autophagy suppresses proliferation of HepG2 cells partially by inhibition of GPC3/wnt/β-catenin signaling.

Keywords: hepatocellular carcinoma, glypican-3, autophagy, proliferation, wnt/β-catenin signaling

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