MIIP is downregulated in gastric cancer and its forced expression inhibits proliferation and invasion of gastric cancer cells in vitro and in vivo
Received 10 July 2018
Accepted for publication 10 November 2018
Published 11 December 2018 Volume 2018:11 Pages 8951—8964
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Tohru Yamada
Dan Sun, Yiwei Wang, Shanshan Jiang, Gang Wang, Yan Xin
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Background: MIIP is associated with cancer progression in various cancers. However, its expression pattern, and associated molecular mechanisms in gastric cancer (GC) progression are still mysterious. We aimed to explore the role of MIIP in proliferation and invasion of GC.
Materials and methods: MIIP expression was evaluated in human GC tissues and cell lines. Public clinical database of GC patients was used to probe the correlation between MIIP expression and prognosis of patients. The effects of forced MIIP expression on GC cells were determined by MTT, cell cycle distribution, colony formation, wound-healing and Transwell assays in vitro, as well as in vivo growth of subcutaneous tumor xenografts and metastasis of xenografted tumors to the lungs in mice. The expressions of GC progression-associated genes, including HOTAIR, MALAT1, HDAC6, AC-tubulin, and cyclin D1, were assessed by Western blotting or qRT-PCR.
Results: Both GC tissues and GC cell lines had lower MIIP expression. Higher level of MIIP in GC tissues predicts better survival in patients. Ectopic expression of MIIP in GC cell lines BGC823 and HGC27 induced G0/G1 cell cycle arrest and inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as the growth of GC xenografts and metastasis of tumors in vivo. Furthermore, overexpression of MIIP suppressed mRNA expressions of HOTAIR and MALAT1, decreased protein expression of HDAC6 and cyclin D1, and elevated AC-tubulin protein expression.
Conclusion: MIIP is a suppressor for GC progression and is a potential therapeutic target for treating GC.
Keywords: MIIP, gastric cancer, proliferation, migration, invasion, metastasis
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