miR-1254 inhibits cell proliferation, migration, and invasion by down-regulating Smurf1 in gastric cancer

• Published in: Cell death & disease 2019-01, Vol.10 (1), p.32-32, Article 32
• Main Authors: Jiang, Mingkun, Shi, Liang, Yang, Chao, Ge, Yugang, Lin, Linling, Fan, Hao, He, Yu, Zhang, Diancai, Miao, Yongchang, Yang, Li
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 13; 13/109; 13/31; 13/44; 13/51; 13/89; 14; 14/28; 14/5; 14/63; 3' Untranslated Regions; 38; 38/32; 38/77; 42; 45/41; 45/44; 59; 631/67/1504/1829; 64/60; 692/53/2421; 82/1; 82/51; AKT protein; Animal models; Animals; Antibodies; Binding Sites; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cholecystokinin; Down-Regulation - genetics; Epithelial-Mesenchymal Transition - genetics; Female; Gastric cancer; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Immunology; Kinases; Life Sciences; Male; Mesenchyme; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Neoplasm Invasiveness; Polymerase chain reaction; Signal transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Therapeutic applications; Transfection; Tumor Burden - genetics; Tumorigenesis; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Wound healing; Xenografts
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-1262-x

Gastric cancer (GC) is one of the most frequent malignancies, and increasing evidence supports the contribution of microRNA (miRNAs) to cancer progression. miR-1254 has been confirmed to participate in the regulation of various cancers, while the function of miR-1254 in GC remains unknown. In this study, we investigated the role of miR-1254 in GC. The expression of miR-1254 was detected in human GC specimens and cell lines by miRNA RT-PCR. The effects of miR-1254 on GC proliferation were determined by CCK-8 proliferation assays, colony formation assays, 5-ethynyl-2′-deoxyuridine (EdU) incorporation, and cell-cycle assays. The ability of migration and invasion was examined by transwell and wound-healing assay. Dual Luciferase reporter assay was used to validate the interaction of miR-1254 with its target gene. The xenograft mouse models were conducted to investigate the effects of miR-1254 in vivo. The signaling pathways and epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot. The results showed that miR-1254 inhibited the proliferation, migration and invasion in vitro and suppressed tumorigenesis in vivo. Smurf1 was shown to be the direct target of miR-1254. Overexpressing Smurf1 could partially counteract the effects caused by miR-1254. Similarly, the effects of the miR-1254-inhibitor were also rescued by Smurf1-shRNA. Furthermore, we found that miR-1254 inhibited EMT and decreased the PI3K/AKT signaling pathway through downregulating Smurf1. In summary, overexpression of miR-1254 could suppress proliferation, migration, invasion, and EMT via PI3K/AKT signaling pathways by downregulation of Smurf1 in GC, which suggests a potential therapeutic target for GC.