Abstract:
: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.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Jiang M,Shi L,Yang C,Ge Y,Lin L,Fan H,He Y,Zhang D,Miao Y,Yang Ldoi
10.1038/s41419-018-1262-xsubject
Has Abstractpub_date
2019-01-10 00:00:00pages
32issue
1issn
2041-4889pii
10.1038/s41419-018-1262-xjournal_volume
10pub_type
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pub_type: 已发布勘误
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