HOTAIR may regulate proliferation, apoptosis, migration and invasion of MCF-7 cells through regulating the P53/Akt/JNK signaling pathway

Biomed Pharmacother. 2017 Jun:90:555-561. doi: 10.1016/j.biopha.2017.03.054. Epub 2017 Apr 10.

Abstract

Breast cancer is a common malignancy, and it is the second leading cause of cancer-related death among women worldwide. The pathogenesis of breast cancer is poorly understood, leading to unsatisfactory efficacy of current anti-PC therapies. The aim of this study is to investigate the role of LncRNA HOTAIR in proliferation, apoptosis, migration and invasion of human breast cancer cell line MCF-7. MCF-7 cells were cultured and transfected with HOTAIR siRNA, and the proliferation rate of cells was determined using MTT and colony-forming assay; moreover, the apoptosis as well as cell cycles were determined using annexin V/propidium iodide staining methods and analyzed using flow cytometery; furthermore, cell scratch and transwell assays have been performed to examine the migration and invasion of MCF-7 cells; Next, cells were collected, and RT-qPCR as well as western blotting assay were performed to examine the expression of P53, MDM2, AKT, JNK, MMP-2 and MMP-9. We discovered that knockdown of HOTAIR induced significant decrease in proliferation and increase in apoptosis of MCF-7 cells, and the cell cycles of HOTAIR siRNA transfected cells have been arrested at G1 phase (p<0.01); moreover, knockdown of HOTAIR lead to marked decrease in the migration and invasion ability of MCF-7 cells; finally, knockdown of HOTAIR induced significant decrease in the expression of P53/Akt/JNK (p<0.01), and significant increase in the expression of P53 in MCF-7 cells (p<0.01). In conclusion, our results proved that HOTAIR may regulate proliferation, apoptosis, migration and invasion of MCF-7 cells through regulating the P53/Akt/JNK signaling pathway.

Keywords: Breast cancer; HOTAIR; P53.

MeSH terms

  • Apoptosis / physiology*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Down-Regulation / physiology
  • Female
  • G1 Phase / physiology
  • Humans
  • MAP Kinase Signaling System / physiology*
  • MCF-7 Cells
  • Neoplasm Invasiveness / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • HOTAIR long untranslated RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt