FBXL19-AS1 promotes cell proliferation and inhibits cell apoptosis via miR-876-5p/FOXM1 axis in breast cancer

Acta Biochim Biophys Sin (Shanghai). 2019 Nov 18;51(11):1106-1113. doi: 10.1093/abbs/gmz110.

Abstract

As the most common cancer and one of the leading causes of cancer-associated mortality, breast cancer continues to need more key molecules to regulate its progression. F-box and leucine-rich repeat protein 19 antisense RNA 1 (known as FBXL19-AS1) is a long non-coding RNA (lncRNA) which has been reported as an oncogene in several types of human cancers. However, the specific downstream targets of FBXL19-AS1 remain unknown. In this study, we set out to find more reliable downstream molecules of FBXL19-AS1 in breast cancer. FBXL19-AS1 was expressed at a high level in breast cancer cells. Loss-of-function experiments revealed that silencing FBXL19-AS1 could impair cell proliferation and induce cell apoptosis in breast cancer. In addition, the location of FBXL19-AS1 in the cytoplasm was detected by fluorescent in situ hybridization assay, while FBXL19-AS1 regulated the expression of Forkhead box M1 (FOXM1) by directly absorbing miR-876-5p. Through rescue assays, it was observed that FOXM1 overexpression recovered the inhibited tumor growth caused by FBXL19-AS1 downregulation. We affirmed the function of FBXL19-AS1 in breast cancer and described the mechanism of the FBXL19-AS1/miR-876-5p/FOXM1 axis. The current work presents the molecular mechanism which underlies FBXL19-AS1 in breast cancer and suggests a comprehensive, feasible FBXL19-AS1-mediated therapeutic approach for treating breast cancer.

Keywords: FBXL19-AS1; FOXM1; breast cancer; miR-876-5p.

MeSH terms

  • Apoptosis
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • F-Box Proteins / genetics
  • F-Box Proteins / physiology*
  • Forkhead Box Protein M1 / metabolism*
  • Humans
  • Loss of Function Mutation
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / physiology*

Substances

  • DNA-Binding Proteins
  • F-Box Proteins
  • FBXL19 protein, human
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MIRN876 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding