Long noncoding RNA LINC00473 functions as a competing endogenous RNA to regulate MAPK1 expression by sponging miR-198 in breast cancer

Pathol Res Pract. 2019 Aug;215(8):152470. doi: 10.1016/j.prp.2019.152470. Epub 2019 May 24.

Abstract

Breast cancer (BC) is one of the primary tumors with high incidence in women. The purpose of this study was to investigate the role of LINC00473 and underlying mechanisms in BC. Expression pattern of LINC00473 was analyzed using qRT-PCR (quantitative real-time polymerase chain reaction) assays in BC tissues and cells. Overexpression or knockdown of LINC00473 in vitro and functional experiments were performed to study its effects on BC cells. Target prediction, luciferase assays, RNA fluorescence in situ hybridization and RNA immunoprecipitation were used to verify the role of LINC00473 as a competing endogenous RNA. The impact of LINC00473 on tumor growth was also evaluated using a xenograft model. In our study, we found that LINC00473 was highly expressed in BC tissues and cells, and the elevated expression was correlated with shorter overall survival in patients with BC. Furthermore, knockdown of LINC00473 significantly inhibited the capacity of proliferation, invasion and migration of BC cells. Animal experiment suggested that silencing LINC00473 could significantly inhibit the tumor growth. Following experiments revealed that LINC00473 may function as a competing endogenous RNA to regulate the expression of Mitogen-Activated Protein Kinase 1 (MAPK1) through competition for miR-198. Thus, increased expression of LINC00473 in breast cancer tissues is linked to poor prognosis. LINC00473 may function as an endogenous completive RNA by sponging miR-198 to regulate MAPK1 expression. Findings of our study contributed to the basis for further exploring the application of LINC00473 as a prognostic and diagnostic biomarker.

Keywords: Breast cancer; LINC00473; MAPK1; miR-198.

MeSH terms

  • Animals
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Prognosis
  • RNA, Long Noncoding / genetics*

Substances

  • LINC00473 RNA, human
  • MIRN198 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1