REG γ knockdown suppresses proliferation by inducing apoptosis and cell cycle arrest in osteosarcoma

Author:

Yin Zhiqiang1,Jin Hao2,Huang Shibo3,Qu Guofan4,Meng Qinggang5

Affiliation:

1. Department of Orthopedics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China

2. Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China

3. Department of General Surgery, Heilongjiang Agricultural Reclamation General Hospital, Harbin, China

4. The Affiliated Tumor Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilong, China

5. Department of Medical Science Institute of Harbin, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilong, China

Abstract

BackgroundOsteosarcoma (OS) is the most common malignant bone tumor with high mortality in children and adolescents. REG γ is overexpressed and plays oncogenic roles in various types of human cancers. However, the expression and potential roles of REG γ in osteosarcoma are elusive. This study aims at exploring possible biological functions of REG γ in the pathogenesis of osteosarcoma and its underlying mechanism.MethodsQuantitativereverse transcription-polymerase chain reaction (qRT-PCR), western blotting andimmunohistochemistry (IHC)were performed to detect the expression levels of REG γ in OS tissues and cell lines. Then, the effects of REG γ expression on OS cell proliferation in vitro were analyzed by Cell Counting Kit-8 (CCK-8), ethylene deoxyuridine (EdU), colony formation, flow cytometry. The protein levels of apoptosis and cell-cycle related proteins were evaluated using western blotting.ResultsIn present study, we found for the first time that REG γ is overexpressed in osteosarcoma tissues and cell lines and knockdown of REG γ significantly inhibits cell proliferation and induces apoptosis and cell cycle arrest in osteosarcoma cells. Furthermore, we observed that p21, caspase-3 and cleaved caspase-3 are increased while the expression of cycinD1 and bcl-2 are decreased after REG γ depletion in osteosarcoma cells. In conclusion, REG γ may be involved in the proliferation of osteosarcoma and serve as a novel therapeutic target in patients with osteosarcoma.

Funder

Natural Science Foundation of Heilongjiang Province, China

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference26 articles.

1. Recent advances in osteosarcoma;Botter;Current Opinion in Pharmacolog,2014

2. Knockdown of REG γ inhibits proliferation by inducing apoptosis and cell cycle arrest in prostate cancer;Chen;American Journal of Translational Research,2017

3. REGgamma deficiency suppresses tumor progression via stabilizing CK1epsilon in renal cell carcinoma;Chen;Cell Death & Disease,2018

4. Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome;Chen;Molecular Cell,2007

5. MEKK3 interacts with the PA28 gamma regulatory subunit of the proteasome;Hagemann;Biochemical Journal,2003

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