MicroRNA-25 promotes gastric cancer proliferation, invasion, and migration by directly targeting F-box and WD-40 Domain Protein 7, FBXW7

• Published in: Tumor biology 2015-09, Vol.36 (10), p.7831-7840
• Main Authors: Gong, Junhua, Cui, Zheng, Li, Li, Ma, Qiang, Wang, Qiufang, Gao, Yinhe, Sun, Hao
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Case-Control Studies; Cell adhesion & migration; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Movement; Cell Proliferation; F-Box Proteins - genetics; F-Box Proteins - metabolism; F-Box-WD Repeat-Containing Protein 7; Female; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; MicroRNAs - genetics; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Real-Time Polymerase Chain Reaction; Research Article; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Survival Rate; Tumor Cells, Cultured; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Xenograft Model Antitumor Assays
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3510-3

Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in tumorigenesis. MiR-25 was previously reported to act as tumor suppressor or oncogene in diverse cancers. However, their expression, function, and mechanism in gastric cancer (GC) are not well known. Here, we show that miR-25 was overexpressed in primary tumor tissues of GC patients and was significantly correlated with a more aggressive phenotype of GC in patients. MiR-25 inhibition significantly decreased the proliferation, invasion, and migration of GC cells in vitro. Furthermore, miR-25 repressed F-box and WD-40 domain protein 7 (FBXW7) expression by directly binding to 3-untranslated region (UTR) of FBXW7, and the inverse correlation was observed between the expressions of miR-25 and FBXW7 mRNA in primary GC tissues. Moreover, the restoration of FBXW7 led to suppressed proliferation, invasion, and migration of GC cells. In vivo, miR-25 promotes tumor growth of GC. Taken together, miR-25 promotes GC progression by directly downregulating FBXW7 expression and may be employed as a novel prognostic marker and therapeutic target of GC.