Downregulation of MiR-1297 predicts poor prognosis and enhances gastric cancer cell growth by targeting CREB1

Biomed Pharmacother. 2018 Sep:105:413-419. doi: 10.1016/j.biopha.2018.05.094. Epub 2018 Jun 2.

Abstract

Dysregulation of mircoRNAs (miRs) that act as tumor suppressors or oncogenes is participated in tumorigenesis and progression. The aim of the study is to investigate the role and mechanism of miR-1297 in gastric cancer (GC). Here, we demonstrated that miR-1297 expression was significantly lower in GC tissue samples compared to adjacent normal tissue samples in 62 cases GC patients. Lower miR-1297 expression positively associated with larger tumor size, lymph node metastasis, advanced TNM stage and poor survival time of patients. Upregulation of miR-1297 significantly inhibited cell proliferation and cell colony forming abilities in vitro. However, downregulation of miR-1297 can cause the reverse biological function changes. In vivo, miR-1297 overexpression suppressed tumor growth. Luciferase reporter assay showed that CREB1 was a direct target of miR-1297 in GC. MiR-1297 inhibited the expression of CREB1 by targeting the 3'UTR of CREB1. Additionally, we demonstrated that CREB1 overexpression rescued the effects on GC cell growth induced by miR-1297. Therefore, these results indicated that miR-1297 might be a prognostic predictor for GC and potential target of GC treatment.

Keywords: CREB1; Cell proliferation; Gastric cancer; Prognosis; miR-1297.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Up-Regulation / genetics

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • MIRN1297 microRNA, human
  • MicroRNAs