Research Papers:
miR-215 promotes malignant progression of gastric cancer by targeting RUNX1
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Abstract
Na Li1,*, Qi-Yue Zhang1,*, Jian-Ling Zou1, Zhong-Wu Li2, Tian-Tian Tian1, Bin Dong2, Xi-Juan Liu3, Sai Ge1, Yan Zhu1, Jing Gao1, Lin Shen1
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
2Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
3Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
*These authors contributed equally to this work
Correspondence to:
Lin Shen, e-mail: [email protected]
Jing Gao, e-mail: [email protected]
Keywords: miR-215, gastric cancer, malignant progression, RUNX1
Received: July 02, 2015 Accepted: November 29, 2015 Published: December 23, 2015
ABSTRACT
Objective: miR-215 was reported to be downregulated and functioned as a tumor suppressor in several cancers. In contrast, miR-215 was preferentially upregulated in gastric cancer (GC) according to our data. Thus, we studied the potential biological function of miR-215 in GC.
Methods: miR-215 expression was measured in 77 paired GC tissues and adjacent non-tumor tissues. Biological functions of miR-215 were analyzed using cell viability, colony formation, migration, invasion, cell cycle, apoptosis and luciferase assays as well as via tumorigenicity and metastasis analysis.
Results: miR-215 was significantly upregulated in 7 GC cell lines and 77 GC tissues compared to adjacent non-tumor tissues (P < 0.05), and miR-215 expression was greater in advanced GC (stage III/IV; P < 0.05). Ectopic expression of miR-215 in GES-1 and HGC-27 cells (low miR-215 expression) promoted cell growth, migration, invasion, and metastasis, and these were reversed in NCI-N87 cells (high miR-215 expression) after miR-215 downregulation. Potential target genes of miR-215 were predicted and RUNX1, a transcription factor and a tumor suppressor, was confirmed to be potential target according to luciferase studies. RUNX1 was downregulated in GC tissues compared to adjacent non-tumor tissues (P < 0.05), and RUNX1 reversed partial function of miR-215 in vitro.
Conclusion: miR-215 promotes malignant progression of GC by targeting RUNX1, and RUNX1 can partially reverse miR-215 effects.
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