The E3 ligase UBR5 regulates gastric cancer cell growth by destabilizing the tumor suppressor GKN1

Journal Article · Fri Sep 30 04:00:00 EDT 2016 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2016.08.170· OSTI ID:22696622

Yang, Min; Jiang, Nan; Cao, Qi-wei ^[1]; Ma, Mao-qiang ^[2]; Sun, Qing ^[1]

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1. Department of Pathology, Qian-fo-shan Hospital Affiliated to Shandong University, No. 16766 Jingshi Road, Jinan, Shandong 250014 (China)
2. Shandong University, No.27, Shanda South Road, Jinan, Shandong 250100 (China)

Gastric cancer is the most common digestive malignant tumor worldwide and the underlying mechanisms are not fully understood. The E3 ligase UBR5 (also known as EDD1) is essentially involved in diverse types of cancer. Here we aimed to study the functions of UBR5 in human gastric cancer. We first analyzed the mRNA and protein levels of UBR5 in human gastric cancer tissues and the results showed that UBR5 was markedly increased in gastric cancer tissues compared with normal gastric mucosa or matched non-cancer gastric tissues. The relationship between UBR5 and survival of gastric cancer patients was analyzed and we found that high UBR5 expression was associated with poor overall and disease-free survival. We further tried to investigate the effects of UBR5 on gastric cancer cell growth in vitro and in vivo. Therefore, we knocked down UBR5 with lentivirus-mediated shRNA and found that UBR5 knockdown repressed in vitro proliferation and colony formation of gastric cancer cells AGS, MG803 and MNK1. In vivo xenograft experiment also demonstrated that UBR5 knockdown inhibited AGS growth. Finally, we explored the mechanism by which UBR5 contributed to the growth of gastric cancer cells. We found that UBR5 bound the tumor suppressor gastrokine 1 (GKN1) and increased its ubiquitination to reduce the protein stability of GKN1. GKN1 knockdown with lentivirus-mediated shRNA increased the in vitro colony formation and in vivo growth of AGS cells, and UBR5 knockdown was unable to affect the colony formation and in vivo growth of AGS cells when GKN1 was knocked down, indicating that GKN1 contributed to the effects of UBR5 in human gastric cancer cells. Taken together, UBR5 plays an essential role in gastric cancer and may be a potential diagnosis and treatment target for gastric cancer. - Highlights: • UBR5 expression is up-regulated in human gastric cancer. • UBR5 overexpression predicts poor survival. • UBR5 regulates gastric cancer growth in vitro and in vivo. • UBR5 reduces the protein stability of GKN1.

• OSTI ID: 22696622
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 478; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
COLONY FORMATION
LIGASES
MUCOUS MEMBRANES
NEOPLASMS
PLANT GROWTH
PLANT TISSUES