Long noncoding RNA OR3A4 promotes metastasis and tumorigenicity in gastric cancer

Oncotarget. 2016 May 24;7(21):30276-94. doi: 10.18632/oncotarget.7217.

Abstract

The contribution of long noncoding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. We used microarray analysis to identify lncRNAs differentially expressed between normal gastric tissues and gastric cancer tissues and validated these differences in quantitative real-time (qRT)-PCR experiments. The expression levels of lncRNA olfactory receptor, family 3, subfamily A, member 4 (OR3A4) were significantly associated with lymphatic metastasis, the depth of cancer invasion, and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by overexpressing and silencing OR3A4 in gastric cancer cells. OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Global microarray analysis combined with RT-PCR, RNA immunoprecipitation, and RNA pull-down analyses after OR3A4 transfection demonstrated that OR3A4 influenced biologic functions in gastric cancer cells via regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. Our results reveal OR3A4 as an oncogenic lncRNA that promotes tumor progression, Therefore, lncRNAs might function as key regulatory hubs in gastric cancer progression.

Keywords: OR3A4; gastric cancer; lncRNA; metastasis; tumorigenesis.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinogenesis / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • LIM Domain Proteins / genetics
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microfilament Proteins / genetics
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Netrins / genetics
  • RNA, Long Noncoding / genetics*
  • Receptors for Activated C Kinase / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Trans-Activators
  • Transcription Factors / genetics
  • Transplantation, Heterologous
  • Tumor Burden / genetics

Substances

  • LIM Domain Proteins
  • MACC1 protein, human
  • Microfilament Proteins
  • NTN4 protein, human
  • Neoplasm Proteins
  • Netrins
  • PDLIM2 protein, human
  • RACK1 protein, human
  • RNA, Long Noncoding
  • Receptors for Activated C Kinase
  • Trans-Activators
  • Transcription Factors