title: miR‑483‑5p promotes growth, invasion and self‑renewal of gastric cancer stem cells by Wnt/β‑catenin signaling.
abstract: Gastric carcinoma (GC) ranks as the second most common cause of cancer‑associated mortality worldwide. Emerging evidence has suggested a potential novel therapeutic strategy based on the ability of cancer stem cells (CSCs) to trigger tumorigenesis. MicroRNAs (miRNAs) have previously been implicated in CSC formation and regulation of their functional characteristics. In the current study, a significant upregulation of miR‑483‑5p levels was demonstrated in spheroid body‑forming cells (P<0.01) by reverse transcription‑quantitative polymerase chain reaction, which were isolated from the MKN‑45 gastric cancer cell line and possessed gastric CSC (GCSC) properties. An MTT assay demonstrated that overexpression of miR‑483‑5p by transfection with miR‑483‑5p mimics significantly increased cell proliferation and Annexin V‑propidium iodide staining indicated the suppression of cell apoptosis, suggesting that miR‑483‑5p has an important function in GCSC growth. Notably, Transwell and sphere formation assays demonstrated that miR‑483‑5p elevation promoted GCSC invasion and cell self‑renewal ability, respectively. Further western blotting assays demonstrated that miR‑483‑5p upregulation induced an increase in the protein expression levels of β‑catenin and its downstream target molecules, including cyclin D1, Bcl‑2 and matrix metalloproteinase 2, indicating that miR‑483‑5p activates Wnt/β‑catenin signaling. Inhibition of this pathway by β‑catenin small interfering RNA transfection attenuated the miR‑483‑5p‑induced effects on cell growth, invasion and self‑renewal. These results demonstrate that miR‑483‑5p may act as an oncogene to promote the development of GC by regulating GCSC growth, invasion and self‑renewal via the Wnt/β‑catenin signaling pathway. Thus, the present study suggests that miR‑483‑5p may be a promising therapeutic target against GC.
authors: Department of General Surgery, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Kai
authors: K
authors: Wu
authors: Department of General Surgery, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Longan
authors: L
authors: Ma
authors: Department of General Surgery, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Jinxiang
authors: J
authors: Zhu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin