title: miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway.
abstract: BACKGROUND
  The aim of this study was to determine the role of miRNA-590-5p in gastric cancer (GC) progression.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction was performed to measure endogenous miR-590-5p levels in GC cells and tissues. Overexpression or knockdown of miR-590-5p in GC cells was performed by transfection with mimics or an inhibitor, respectively. MTT, matrigel transwell, and Western blot assays were used to assess the effects of miR-590-5p on cell proliferation, invasion, chemosensitivity of GC cells, and the AKT pathway, respectively. In silico prediction and luciferase reporter activity were used to identify potential targets of miR-590-5p. A xenograft model was also established to evaluate the function of miR-590-5p in vivo.
  
  
  RESULTS
  The expression of miR-590-5p was significantly increased in GC cells and tissues, and upregulated miR-590-5p was associated with increased tumor size, lymph node metastasis, and poor survival. Overexpression of miR-590-5p promoted cell proliferation and invasion and reduced the sensitivity of GC cells to cisplatin and paclitaxel. In contrast, inhibition of miR-590-5p had the opposite effects on GC cells. RECK was identified as a direct target of miR-590-5p. Knockdown of RECK accelerated cell proliferation and motility and decreased the drug sensitivity. Furthermore, reintroduction of RECK inhibited the oncogenic effects of miR-590-5p by suppressing cell proliferation and invasion and increasing drug sensitivity. We found that the AKT/ERK and STAT3 signaling pathways were activated by miR-590-5p overexpression. The chemoresistance of miR-590-5p was also verified by in vivo analysis.
  
  
  CONCLUSIONS
  In summary, we suggest that the miR-590-5p/RECK/AKT axis contributes to GC and may serve as a promising therapeutic target for treatment.
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Xiaoyou
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Feng
keywords: AKT pathway; RECK; gastric cancer; invasion; miR-590; prognosis