Abstract
ObjectivemiR-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.MethodsmiR-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.ResultsmiR-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.ConclusionmiR-215 promotes malignant progression of GC by targeting RUNX1, and RUNX1 can partially reverse miR-215 effects.
Highlights
Gastric cancer (GC) is one of the three most common cancers in Japan, South Korea, and in China, where it is most prevalent and represents 47% of new annual cancer cases worldwide
We found that miR-215 was downregulated in colorectal cancer and patients with miR-215 high expression had lower 3-year relapse rate and longer median disease-free survival (DFS) compared with patients with miR-215 low expression [6]
We found that miR-215 was preferentially upregulated in GC according to our data (Figure 1A), indicating a potential role for miR-215 in gastric carcinogenesis
Summary
Gastric cancer (GC) is one of the three most common cancers in Japan, South Korea, and in China, where it is most prevalent and represents 47% of new annual cancer cases worldwide. Researches have revealed that microRNAs (miRNAs) are important for the development and progression of multiple tumors including GC via regulation of several pivotal target genes [3,4,5]. Previous work suggested that miR-215 was downregulated and functioned as a potential tumor www.impactjournals.com/oncotarget suppressor in several cancers including colorectal cancer [6,7,8] and esophageal adenocarcinoma [9]. Deng Y et al [10] performed miRNA microarray in six primary gastric tumors and their matched nonmalignant tissues and found that miR-215 was the most upregulated miRNA. We found that miR-215 was preferentially upregulated in GC according to our data (Figure 1A), indicating a potential role for miR-215 in gastric carcinogenesis. Deng and colleagues reported that miR-215 was upregulated in GC and promoted cell proliferation in vitro via targeting RB1 and ALCAM [10, 11]
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