UCA1 promotes cell proliferation and invasion of gastric cancer by targeting CREB1 sponging to miR-590-3p

Cancer Med. 2018 Apr;7(4):1253-1263. doi: 10.1002/cam4.1310. Epub 2018 Mar 8.

Abstract

Long noncoding RNAs (lncRNAs) have emerged as regulators in a variety of biological processes, including carcinogenesis in human cancer. UCA1 has been reported to be upregulated in gastric cancer (GC); however, the underlying functional roles of UCA1 in GC have not been established. In the current study, we showed that UCA1 is significantly higher in GC tissues and cells compared with adjacent normal tissues and a gastric epithelium cell line, respectively. Higher UCA1 expression was associated with lymph node metastasis, TNM stage, and poor overall survival (OS) in GC patients. In vitro functional studies confirmed that UCA1 promotes cell proliferation, colony formation ability, and cell invasion in GC cells. We demonstrated that knockdown of UCA1 inhibits tumor growth in vivo. The double luciferase reporter, RNA-binding protein immunoprecipitation assay, and RNA pull down assay demonstrated that miR-590-3p serves as a target for UCA1. UCA1 promoted cell proliferation and invasion by negatively regulating miR-590-3p expression. Moreover, we demonstrated that CREB1 is a downstream target of miR-590-3p and UCA1 activates CREB1 expression by sponging to miR-590-3p. Thus, these results showed that UCA1 functions as an oncogene in GC and may be a target for treatment of GC.

Keywords: CREB1; UCA1; gastric cancer; miR-590-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA Interference*
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • MIRN590 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • UCA1 RNA, human